Bioengineered T cell mediated immunity, materials and other methods for modulating cluster of differentiation IV and/or VIII

Information

  • Patent Grant
  • 11926667
  • Patent Number
    11,926,667
  • Date Filed
    Tuesday, October 12, 2021
    2 years ago
  • Date Issued
    Tuesday, March 12, 2024
    2 months ago
Abstract
Provided herein, in certain aspects, are antibodies that bind to CD8, as well as recombinant cells containing the vectors, and compositions comprising the antibodies. Also provided herein, in certain aspects, are antibodies that bind to CD4, as well as recombinant cells containing the vectors, and compositions comprising the antibodies. Also provided herein, in certain aspects, are multispecific antibodies that bind to CD4 and CD8, as well as recombinant cells containing the vectors, and compositions comprising the antibodies. Methods of making the antibodies are also provided.
Description
FIELD

Provided herein, in certain aspects, are antibodies that bind to CD4, as well as recombinant cells containing the vectors, and compositions comprising the antibodies. Also provided herein, in certain aspects, are antibodies that bind to CD8, as well as recombinant cells containing the vectors, and compositions comprising the antibodies. Also provided herein, in certain aspects, are multispecific antibodies that bind to CD4 and CD8, as well as recombinant cells containing the vectors, and compositions comprising the antibodies. Methods of making and using the antibodies are also provided.


REFERENCE TO SEQUENCE LISTING SUBMITTED ELECTRONICALLY

This application contains a sequence listing, which is submitted electronically via EFS-Web as an ASCII formatted sequence listing with a file name of “14620-269-999_SL.txt” and a creation date of Oct. 7, 2021 and having a size of 1,812,825 bytes. The sequence listing submitted via EFS-Web is part of the specification and is herein incorporated by reference in its entirety.


SUMMARY

In one aspect, provided herein is an antibody that binds CD8. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:31; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:32. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:65; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:66. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:99; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:100. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:133; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:134. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:167; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:168. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:201; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:202. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:235; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:236. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:269; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:270. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:303; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:304. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:337; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:338. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:371; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:372. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:405; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:406. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:439; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:440. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:473; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:474. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:507; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:508. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:541; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:542. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:575; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:576. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:609; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:610. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:643; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:644. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:677; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:678. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:711; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:712. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:745; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:746. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:779; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:780. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:813; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:814. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:847; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:848. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:881; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:882. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:915; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:916. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:949; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:950. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:983; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:984. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1017; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1018. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1051; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1052. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1085; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1086. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1119; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1120. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1153; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1154. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1187; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1188. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1221; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1222. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1255; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1256. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1289; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1290. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1323; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1324. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1357; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1358. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1391; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1392. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1425; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1426. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1459; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1460. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1493; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1494. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1527; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1528. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1561; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1562. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1595; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1596. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1629; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1630. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1663; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1664. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1697; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1698. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1731; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1732. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1765; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1766. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1799; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1800. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1833; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1834. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1867; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1868. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1901; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1902. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1935; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1936. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1969; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1970. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2003; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2004. In another aspect, provided herein is an antibody that binds CD8. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2037; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2038. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2071; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2072. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2105; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2106. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2139; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2140. In one embodiment, the CD8 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2173; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2174.


In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the CD8 antibody are according to the Kabat numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the CD8 antibody are according to the Chothia numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the CD8 antibody are according to the AbM numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the CD8 antibody are according to the Contact numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the CD8 antibody are according to the IMGT numbering system.


In some embodiments, the antibody binds a CD8 antigen. In some embodiments, antibody binds a CD8 epitope. In some embodiments, the antibody specifically binds to CD8. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 form a binding site for an antigen of the CD8. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 form a binding site for an epitope of the CD8. In some embodiments, the CD8 is present on the surface of a T cell.


In some embodiments, the antibody binds to CD8a. In some embodiments, the antibody binds a CD8a antigen. In some embodiments, antibody binds a CD8a epitope. In some embodiments, the antibody specifically binds to CD8a. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 form a binding site for an antigen of the CD8a. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 form a binding site for an epitope of the CD8a. In some embodiments, the CD8a is present on the surface of a T cell.


In some embodiments, the antibody binds to CD8β. In some embodiments, the antibody binds a CD8β antigen. In some embodiments, antibody binds a CD8β epitope. In some embodiments, the antibody specifically binds to CD8β. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 form a binding site for an antigen of the CD8β. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 form a binding site for an epitope of the CD8β. In some embodiments, the CD8β is present on the surface of a T cell.


In some embodiments, the antibody binds at the interface of CD8α and CD8p. In some embodiments, the antibody binds an antigen at the interface of CD8α and CD8β. In some embodiments, antibody binds an epitope at the interface of CD8α and CD8β. In some embodiments, the antibody specifically binds at the interface of CD8α and CD8β. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 form a binding site for an antigen at the interface of CD8α and CD8β. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 form a binding site for an epitope at the interface of CD8α and CD8β. In some embodiments, the interface of CD8α and CD8β is present on the surface of a T cell.


In some embodiments, the CD8 antibody is a humanized antibody. In some embodiments, the antibody is an IgG antibody. In some embodiments, the CD8 antibody is an IgG1 antibody. In some embodiments, the CD8 antibody is an IgG2 antibody. In some embodiments, the CD8 antibody is an IgG3 antibody. In some embodiments, the CD8 antibody is an IgG4 antibody. In some embodiments, the CD8 antibody comprises a kappa light chain. In some embodiments, the CD8 the antibody comprises a lambda light chain. In some embodiments, the CD8 antibody is a monoclonal antibody. In some embodiments, the CD8 antibody is multivalent. In some embodiments, the CD8 antibody is capable of binding at least three antigens. In some embodiments, the CD8 antibody is capable of binding at least four antigens. In some embodiments, the CD8 antibody is capable of binding at least five antigens. In some embodiments, the CD8 antibody is a multispecific antibody. In some embodiments, the CD8 antibody is a bispecific antibody. In some embodiments, the CD8 antibody is a trispecific antibody. In some embodiments, the CD8 antibody is a quadraspecific antibody.


In some embodiments, the multispecific CD8 antibody comprises: (i) a first binding domain that binds CD8, and a second binding domain that binds to a second target; (ii) a first binding domain that binds CD8, a second binding domain that binds to a second target, and a third binding domain that binds to a third target; or (iii) a first binding domain that binds CD8, and a second binding domain that binds to a second target, a third binding domain that binds to a third target, and a fourth binding domain that binds to a fourth target. In some embodiments, the second target is CD4. In some embodiments, the second target is a T cell receptor (TCR) complex, CD3, CD3ε, CD3γ, CD3δ, CD3ζ, a TCRα chain, a TCRβ chain, a TCRγ chain, or a TCRδ chain. In some embodiments, the second target is a T cell costimulatory molecule, CD28, CTLA4, ICOS, 4-1BB, GITR, CD27, OX40, CD40L, HVEM, Galectin-9, TIM-1, LFA1, CD2 or PD1. In some embodiments, the second target is CD4; and the third target is a TCR complex, CD3, CD3ε, CD3γ, CD3δ, CD3ζ, a TCRα chain, a TCRβ chain, a TCRγ chain, a TCRδ chain. In some embodiments, the second target is CD4; and the third target is a T cell costimulatory molecule, CD28, CTLA4, ICOS, 4-1BB, GITR, CD27, OX40, CD40L, HVEM, Galectin-9, TIM-1, LFA1, CD2, or PD1. In some embodiments, the second target is a TCR complex, CD3, CD3ε, CD3γ, CD3δ, CD3ζ, a TCRα chain, a TCRβ chain, a TCRγ chain, or a TCRδ chain; and the third target is a T cell costimulatory molecule, CD28, CTLA4, ICOS, 4-1BB, GITR, CD27, OX40, CD40L, HVEM, Galectin-9, TIM-1, LFA1, CD2, or PD1. In some embodiments, the second target is CD4; wherein the third target is a TCR complex, CD3, CD3ε, CD3γ, CD3δ, CD3ζ, a TCRα chain, a TCRβ chain, a TCRγ chain, or a TCRδ chain; and wherein the fourth target is a T cell costimulatory molecule, CD28, CTLA4, ICOS, 4-1BB, GITR, CD27, OX40, CD40L, HVEM, Galectin-9, TIM-1, LFA1, CD2, or PD1.


Also provided herein is a multispecific CD8 antibody, wherein the multispecific CD8 antibody comprises: a first binding domain that binds CD8, and a second binding domain that binds to a second target, a third binding domain that binds to a third target, and a fourth binding domain that binds to a fourth target. In some embodiments, the second target is CD4, the third target is a TCR complex, and the fourth target is a T cell costimulatory molecule. In some embodiments, the third target is CD3. In some embodiments, the third target is CD3ε. In some embodiments, the third target is CD3γ. In some embodiments, the third target is CD3δ. In some embodiments, the third target is CD3ζ. In some embodiments, the third target is a TCRα chain. In some embodiments, the third target is a TCRβ chain. In some embodiments, the third target is a TCRγ chain. In some embodiments, the third target is a TCRδ chain. In some embodiments, the fourth target is CD28. In some embodiments, the fourth target is CTLA4. In some embodiments, the fourth target is ICOS. In some embodiments, the fourth target is 4-1BB. In some embodiments, the fourth target is GITR. In some embodiments, the fourth target is CD27. In some embodiments, the fourth target is OX40. In some embodiments, the fourth target is CD40L. In some embodiments, the fourth target is HVEM. In some embodiments, the fourth target is Galectin-9. In some embodiments, the fourth target is TIM-1. In some embodiments, the fourth target is LFA1. In some embodiments, the fourth target is CD2. In some embodiments, the fourth target is PD1.


Also provided herein is a multispecific CD8 antibody, wherein the multispecific CD8 antibody comprises: a first binding domain that binds CD8, and a second binding domain that binds to CD4.


In a specific embodiments, provided is a multispecific antibody, wherein the multispecific antibody comprises: a first binding domain that binds to CD8 and a second binding domain that binds to CD4. In a certain embodiments, the first binding domain that binds to CD8 is a CD8 antibody provided herein. In other embodiments, the second binding domain that binds to CD4 is a CD4 antibody provided herein. In specific embodiments, the first binding domain that binds to CD8 is a CD8 antibody provided herein, and the second binding domain that binds to CD4 is a CD4 antibody provided herein. In certain embodiments, the multispecific antibody further binds a third target as provided herein. In other embodiments, the multispecific antibody further binds a third target as provided herein and a fourth target as provided herein.


Also provided herein is a multispecific CD8 antibody, wherein the multispecific CD8 antibody comprises a first binding domain that binds CD8, a second binding domain that binds to a second target, and a third binding domain that binds to a third target. In some embodiments, the second target is a TCR complex, and the third target is a T cell costimulatory molecule. In some embodiments, the second target is CD3. In some embodiments, the second target is CD3ε. In some embodiments, the second target is CD3γ. In some embodiments, the second target is CD3δ. In some embodiments, the second target is CD3ζ. In some embodiments, the second target is a TCRα chain. In some embodiments, the second target is a TCRβ chain. In some embodiments, the second target is a TCRγ chain. In some embodiments, the second target is a TCRδ chain. In some embodiments, the third target is CD28. In some embodiments, the third target is CTLA4. In some embodiments, the third target is ICOS. In some embodiments, the third target is 4-1BB. In some embodiments, the third target is GITR. In some embodiments, the third target is CD27. In some embodiments, the third target is OX40. In some embodiments, the third target is CD40L. In some embodiments, the third target is HVEM. In some embodiments, the third target is Galectin-9. In some embodiments, the third target is TIM-1. In some embodiments, the third target is LFA1. In some embodiments, the third target is CD2. In some embodiments, the third target is PD1.


In another aspect, provided is a nucleic acid encoding a CD8 antibody provided herein. Also provided is a vector comprising a nucleic acid encoding a CD8 antibody provided herein. Also provided is a host cell comprising a vector comprising a nucleic acid encoding a CD8 antibody provided herein. Also provided is a kit comprising vector comprising a nucleic acid encoding a CD8 antibody provided herein, and packaging for the same.


In another aspect, provided is a kit comprising a CD8 antibody provided herein, and packaging for the same.


In another aspect, provided is a pharmaceutical composition comprising a CD8 antibody provided herein, and a pharmaceutically acceptable carrier.


In another aspect, provided is a method of producing a pharmaceutical composition comprising a CD8 antibody provided herein, comprising combining the CD8 antibody with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition.


In another aspect, provided is a method of activating a T cell expressing CD8, comprising contacting the T cell with a CD8 antibody provided herein. In certain embodiments, the contacting results in an increase in CD69, CD25, and/or Granzyme B expression, as compared to a control T cell expressing CD8.


In another aspect, provided is a method of enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting a CD8-expressing cell comprising: providing a sample comprising the CD8-expressing cell; contacting the sample with the CD8 antibody provided herein; and enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD8-expressing cell bound to the CD8 antibody. In another aspect, provided is a method of enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting a CD8-expressing cell comprising: contacting a CD8-expressing cell with the CD8 antibody provided herein; and enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD8-expressing cell bound to the CD8 antibody. In another aspect, provided is a method of enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting a CD8-expressing cell comprising: contacting a CD8-expressing cell with the CD8 antibody provided herein; and enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD8-expressing cell based on binding of the CD8-expressing cell to the CD8 antibody. In some embodiments, the CD8-expressing cell is a T cell. In some embodiments, the CD8-expressing cell is a CD8+ cytotoxic T lymphocyte (CTL). In some embodiments, the CD8-expressing cell is provided as a sample comprising a population of cells. In some embodiments, the cells are lymphocytes. In some embodiments, the cells are T cells. In some embodiments, the sample is a blood sample. In some embodiments, the sample is a tissue sample. In some embodiments, the CD8 antibody is a multispecific CD8 antibody provided herein.


In another aspect, provided herein is an antibody that binds CD4. In one embodiment, the CD4 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2207; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2208. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2241; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2242. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2275; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2276. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2309; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2310. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2343; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2344. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2377; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2378. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2411; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2412. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2445; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2446. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2479; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2480. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2513; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2514. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2547; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2548. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2581; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2582. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2615; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2616. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2649; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2650. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2683; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2684. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2717; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2718. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2751; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2752. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2785; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2786. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2819; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2820. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2853; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2854. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2887; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2888. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2921; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2922. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2955; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2956. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2989; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2990. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3023; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3024. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3057; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3058. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3091; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3092. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3125; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3126. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3159; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3160. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3193; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3194. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3227; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3228. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3261; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3262. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3295; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3296. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3329; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3330. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3363; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3364. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3397; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3398. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3431; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3432. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3465; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3466. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3499; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3500. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3533; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3534. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3567; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3568. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3601; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3602. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3635; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3636. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3669; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3670. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3703; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3704. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3737; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3738. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3771; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3772. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3805; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3806. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3839; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3840. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3873; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3874. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3907; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3908. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3941; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3942. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3975; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3976. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4009; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4010. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4043; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4044. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4077; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4078. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4111; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4112. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4145; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4146. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4179; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4180. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4213; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4214. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4247; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4248. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4281; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4282. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4315; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4316. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4349; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4350. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4383; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4384. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4417; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4418. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4451; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4452. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4485; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4486. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4519; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4520. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4553; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4554. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4587; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4588. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4621; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4622. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4655; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4656. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4689; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4690. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4723; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4724. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4757; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4758. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4791; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4792. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4825; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4826. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4859; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4860. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4893; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4894. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4927; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4928. In one embodiment, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4961; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4962.


In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the CD4 antibody are according to the Kabat numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the CD4 antibody are according to the Chothia numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the CD4 antibody are according to the AbM numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the CD4 antibody are according to the Contact numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the CD4 antibody are according to the IMGT numbering system.


In some embodiments, the antibody binds a CD4 antigen. In some embodiments, antibody binds a CD4 epitope. In some embodiments, the antibody specifically binds to CD4. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 form a binding site for an antigen of the CD4. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 form a binding site for an epitope of the CD4. In some embodiments, the CD4 is present on the surface of a T cell.


In some embodiments, the CD4 antibody is a humanized antibody. In some embodiments, the antibody is an IgG antibody. In some embodiments, the CD4 antibody is an IgG1 antibody. In some embodiments, the CD4 antibody is an IgG2 antibody. In some embodiments, the CD4 antibody is an IgG3 antibody. In some embodiments, the CD4 antibody is an IgG4 antibody. In some embodiments, the CD4 antibody comprises a kappa light chain. In some embodiments, the CD4 the antibody comprises a lambda light chain. In some embodiments, the CD4 antibody is a monoclonal antibody. In some embodiments, the CD4 antibody is multivalent. In some embodiments, the CD4 antibody is capable of binding at least four antigens. In some embodiments, the CD4 antibody is capable of binding at least five antigens. In some embodiments, the CD4 antibody is a multispecific antibody. In some embodiments, the CD4 antibody is a bispecific antibody. In some embodiments, the CD4 antibody is a trispecific antibody. In some embodiments, the CD4 antibody is a quadraspecific antibody.


In some embodiments, the multispecific CD4 antibody comprises: (i) a first binding domain that binds CD4, and a second binding domain that binds to a second target; (ii) a first binding domain that binds CD4, a second binding domain that binds to a second target, and a third binding domain that binds to a third target; or (iii) a first binding domain that binds CD4, and a second binding domain that binds to a second target, a third binding domain that binds to a third target, and a fourth binding domain that binds to a fourth target. In some embodiments, the second target is CD8. In some embodiments, the second target is CD8 and the second binding domain binds CD8α. In some embodiments, the second target is CD8 and the second binding domain binds CD8β. In some embodiments, the second target is CD8 and the second binding domain binds at the interface of CD8α and CD8β. In some embodiments, the second target is a T cell receptor (TCR) complex, CD3, CD3ε, CD3γ, CD3δ, CD3ζ, a TCRα chain, a TCRβ chain, a TCRγ chain, or a TCRδ chain. In some embodiments, the second target is a T cell costimulatory molecule, CD28, CTLA4, ICOS, 4-1BB, GITR, CD27, OX40, CD40L, HVEM, Galectin-9, TIM-1, LFA1, CD2, or PD1. In some embodiments, the second target is CD8; and the third target is a TCR complex, CD3, CD3ε, CD3γ, CD3δ, CD3ζ, a TCRα chain, a TCRβ chain, a TCRγ chain, a TCRδ chain. In some embodiments, the second target is CD8; and the third target is a T cell costimulatory molecule, CD28, CTLA4, ICOS, 4-1BB, GITR, CD27, OX40, CD40L, HVEM, Galectin-9, TIM-1, LFA1, CD2, or PD1. In some embodiments, the second target is a TCR complex, CD3, CD3ε, CD3γ, CD3δ, CD3ζ, a TCRα chain, a TCRβ chain, a TCRγ chain, or a TCRδ chain; and the third target is a T cell costimulatory molecule, CD28, CTLA4, ICOS, 4-1BB, GITR, CD27, OX40, CD40L, HVEM, Galectin-9, TIM-1, LFA1, CD2, or PD1. In some embodiments, the second target is CD8; wherein the third target is a TCR complex, CD3, CD3ε, CD3γ, CD3δ, CD3ζ, a TCRα chain, a TCRβ chain, a TCRγ chain, or a TCRδ chain; and wherein the fourth target is a T cell costimulatory molecule, CD28, CTLA4, ICOS, 4-1BB, GITR, CD27, OX40, CD40L, HVEM, Galectin-9, TIM-1, LFA1, CD2, or PD1.


Also provided herein is a multispecific CD4 antibody, wherein the multispecific CD4 antibody comprises: a first binding domain that binds CD4, and a second binding domain that binds to a second target, a third binding domain that binds to a third target, and a fourth binding domain that binds to a fourth target. In some embodiments, the second target is CD8, the third target is a TCR complex, and the fourth target is a T cell costimulatory molecule. In some embodiments, the third target is CD3. In some embodiments, the third target is CD3ε. In some embodiments, the third target is CD3γ. In some embodiments, the third target is CD3δ. In some embodiments, the third target is CD3ζ. In some embodiments, the third target is a TCRα chain. In some embodiments, the third target is a TCRβ chain. In some embodiments, the third target is a TCRγ chain. In some embodiments, the third target is a TCRδ chain. In some embodiments, the fourth target is CD28. In some embodiments, the fourth target is CTLA4. In some embodiments, the fourth target is ICOS. In some embodiments, the fourth target is 4-1BB. In some embodiments, the fourth target is GITR. In some embodiments, the fourth target is CD27. In some embodiments, the fourth target is OX40. In some embodiments, the fourth target is CD40L. In some embodiments, the fourth target is HVEM. In some embodiments, the fourth target is Galectin-9. In some embodiments, the fourth target is TIM-1. In some embodiments, the fourth target is LFA1. In some embodiments, the fourth target is CD2. In some embodiments, the fourth target is PD1.


Also provided herein is a multispecific CD4 antibody, wherein the multispecific CD4 antibody comprises: a first binding domain that binds CD4, and a second binding domain that binds to CD8.


Also provided herein is a multispecific CD4 antibody, wherein the multispecific CD4 antibody comprises a first binding domain that binds CD4, a second binding domain that binds to a second target, and a third binding domain that binds to a third target. In some embodiments, the second target is a TCR complex, and the third target is a T cell costimulatory molecule. In some embodiments, the second target is CD3. In some embodiments, the second target is CD3ε. In some embodiments, the second target is CD3γ. In some embodiments, the second target is CD3δ. In some embodiments, the second target is CD3ζ. In some embodiments, the second target is a TCRα chain. In some embodiments, the second target is a TCRβ chain. In some embodiments, the second target is a TCRγ chain. In some embodiments, the second target is a TCRδ chain. In some embodiments, the third target is CD28. In some embodiments, the third target is CTLA4. In some embodiments, the third target is ICOS. In some embodiments, the third target is 4-1BB. In some embodiments, the third target is GITR. In some embodiments, the third target is CD27. In some embodiments, the third target is OX40. In some embodiments, the third target is CD40L. In some embodiments, the third target is HVEM. In some embodiments, the third target is Galectin-9. In some embodiments, the third target is TIM-1. In some embodiments, the third target is LFA1. In some embodiments, the third target is CD2. In some embodiments, the third target is PD1.


In another aspect, provided is a nucleic acid encoding a CD4 antibody provided herein. Also provided is a vector comprising a nucleic acid encoding a CD4 antibody provided herein. Also provided is a host cell comprising a vector comprising a nucleic acid encoding a CD4 antibody provided herein. Also provided is a kit comprising vector comprising a nucleic acid encoding a CD4 antibody provided herein, and packaging for the same.


In another aspect, provided is a kit comprising a CD4 antibody provided herein, and packaging for the same.


In another aspect, provided is a pharmaceutical composition comprising a CD4 antibody provided herein, and a pharmaceutically acceptable carrier.


In another aspect, provided is a method of producing a pharmaceutical composition comprising a CD4 antibody provided herein, comprising combining the CD4 antibody with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition.


In another aspect, provided is a method of activating a T cell expressing CD4, comprising contacting the T cell with a CD4 antibody provided herein. In certain embodiments, the contacting results in an increase in CD69, CD25, and/or Granzyme B expression, as compared to a control T cell expressing CD4.


In another aspect, provided is a method of enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting a CD4-expressing cell comprising: providing a sample comprising the CD4-expressing cell; contacting the sample with the CD4 antibody provided herein; and enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD4-expressing cell bound to the CD4 antibody. In another aspect, provided is a method of enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting a CD4-expressing cell comprising: contacting a CD4-expressing cell with the CD4 antibody provided herein; and enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD4-expressing cell bound to the CD4 antibody. In another aspect, provided is a method of enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting a CD4-expressing cell comprising: contacting a CD4-expressing cell with the CD4 antibody provided herein; and enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD4-expressing cell based on binding of the CD4-expressing cell to the CD4 antibody. In some embodiments, the CD4-expressing cell is a T cell. In some embodiments, the CD4-expressing cell is a CD4+ T helper cell. In some embodiments, the CD4-expressing cell is provided as a sample comprising a population of cells. In some embodiments, the cells are lymphocytes. In some embodiments, the cells are T cells. In some embodiments, the sample is a blood sample. In some embodiments, the sample is a tissue sample. In some embodiments, the CD4 antibody is a multispecific CD4 antibody provided herein.


In another aspect, provided is a multispecific antibody, wherein the multispecific antibody comprises: a first binding domain that binds to CD8 and a second binding domain that binds to CD4 (i.e., a multispecific CD4/CD8 antibody). In a certain embodiments, the first binding domain that binds to CD8 is a CD8 antibody provided herein. In other embodiments, the second binding domain that binds to CD4 is a CD4 antibody provided herein. In specific embodiments, the first binding domain that binds to CD8 is a CD8 antibody provided herein, and the second binding domain that binds to CD4 is a CD4 antibody provided herein. In certain embodiments, the multispecific antibody further binds a third target as provided herein. In other embodiments, the multispecific antibody further binds a third target as provided herein and a fourth target as provided herein.


In some embodiments of multispecific CD4/CD8 antibody provided herein, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the Kabat numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the Chothia numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the AbM numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the Contact numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the IMGT numbering system.


In some embodiments of multispecific CD4/CD8 antibody provided herein, the antibody is a humanized antibody. In some embodiments, the antibody is an IgG antibody. In some embodiments, the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody. In some embodiments, the antibody comprises a kappa light chain. In some embodiments, the antibody comprises a lambda light chain. In some embodiments, the antibody is a monoclonal antibody.


In some embodiments of multispecific CD4/CD8 antibody provided herein, the first binding domain binds a CD8 antigen. In some embodiments, the first binding domain binds a CD8 epitope. In some embodiments, the first binding domain specifically binds to CD8. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the first binding domain form a binding site for an antigen of the CD8. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the first binding domain form a binding site for an epitope of the CD8. In some embodiments, the CD8 is present on the surface of a T cell.


In some embodiments of multispecific CD4/CD8 antibody provided herein, the second binding domain binds a CD4 antigen. In some embodiments, the second binding domain binds a CD4 epitope. In some embodiments, the second binding domain specifically binds to CD4. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the second binding domain form a binding site for an antigen of the CD4. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the second binding domain form a binding site for an epitope of the CD4. In some embodiments, the CD4 is present on the surface of a T cell.


In some embodiments of multispecific CD4/CD8 antibody provided herein, the antibody is multivalent. In some embodiments, the antibody is capable of binding at least three antigens. In some embodiments, the antibody is capable of binding at least four antigens. In some embodiments, the antibody is capable of binding at least five antigens.


In some embodiments of multispecific CD4/CD8 antibody provided herein, the antibody is a bispecific antibody. In some embodiments, the antibody is a trispecific antibody. In some embodiments, the antibody is a quadraspecific antibody.


In some embodiments of multispecific CD4/CD8 antibody provided herein, the multispecific antibody further comprises: a third binding domain that binds to a third target. In some embodiments, the third target is a TCR complex. In some embodiments, the third target is CD3. In some embodiments, the third target is CD3ε. In some embodiments, the third target is CD3γ. In some embodiments, the third target is CD3δ. In some embodiments, the third target is CD3ζ. In some embodiments, the third target is a TCRα chain. In some embodiments, the third target is a TCRβ chain. In some embodiments, the third target is a TCRγ chain. In some embodiments, the third target is a TCRδ chain. In some embodiments, the third target is CD28. In some embodiments, the third target is CTLA4. In some embodiments, the third target is ICOS. In some embodiments, the third target is 4-1BB. In some embodiments, the third target is GITR. In some embodiments, the third target is CD27. In some embodiments, the third target is OX40. In some embodiments, the third target is CD40L. In some embodiments, the third target is HVEM. In some embodiments, the third target is Galectin-9. In some embodiments, the third target is TIM-1. In some embodiments, the third target is LFA1. In some embodiments, the third target is CD2. In some embodiments, the third target is PD1.


In some embodiments of multispecific CD4/CD8 antibody provided herein, the multispecific antibody further comprises: a third binding domain that binds to a third target, and a fourth binding domain that binds to a fourth target. In some embodiments, the third target is a TCR complex. In some embodiments, the third target is CD3. In some embodiments, the third target is CD3ε. In some embodiments, the third target is CD3γ. In some embodiments, the third target is CD3δ. In some embodiments, the third target is CD3ζ. In some embodiments, the third target is a TCRα chain. In some embodiments, the third target is a TCRβ chain. In some embodiments, the third target is a TCRγ chain. In some embodiments, the third target is a TCRδ chain. In some embodiments, the fourth target is CD28. In some embodiments, the fourth target is CTLA4. In some embodiments, the fourth target is ICOS. In some embodiments, the fourth target is 4-1BB. In some embodiments, the fourth target is GITR. In some embodiments, the fourth target is CD27. In some embodiments, the fourth target is OX40. In some embodiments, the fourth target is CD40L. In some embodiments, the fourth target is HVEM. In some embodiments, the fourth target is Galectin-9. In some embodiments, the fourth target is TIM-1. In some embodiments, the fourth target is LFA1. In some embodiments, the fourth target is CD2. In some embodiments, the fourth target is PD1.


In another aspect, provided is a nucleic acid encoding a multispecific CD4/CD8 antibody provided herein. Also provided is a vector comprising a nucleic acid encoding a multispecific CD4/CD8 antibody provided herein. Also provided is a host cell comprising a vector comprising a nucleic acid encoding a multispecific CD4/CD8 antibody provided herein. Also provided is a kit comprising vector comprising a nucleic acid encoding a multispecific CD4/CD8 antibody provided herein, and packaging for the same.


In another aspect, provided is a kit comprising a multispecific CD4/CD8 antibody provided herein, and packaging for the same.


In another aspect, provided is a pharmaceutical composition comprising a multispecific CD4/CD8 antibody provided herein, and a pharmaceutically acceptable carrier.


In another aspect, provided is a method of producing a pharmaceutical composition comprising a multispecific CD4/CD8 antibody provided herein, comprising combining the multispecific CD4/CD8 antibody with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition.


In another aspect, provided is a method of enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting CD4-expressing cells and/or CD8-expressing cells comprising: providing a sample comprising the CD4-expressing cells and/or CD8-expressing cells; contacting the sample with the multispecific CD4/CD8 antibody provided herein; and enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD4-expressing cells and/or CD8-expressing cells bound to the multispecific CD4/CD8 antibody. In another aspect, provided is a method of enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting a CD4-expressing cells and/or CD8-expressing cells comprising: contacting a CD4-expressing cells and/or CD8-expressing cells with the multispecific CD4/CD8 antibody provided herein; and enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD4-expressing cells and/or CD8-expressing cells bound to the multispecific CD4/CD8 antibody. In another aspect, provided is a method of enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting a CD4-expressing cells and/or CD8-expressing cells comprising: contacting a CD4-expressing cells and/or CD8-expressing cells with the multispecific CD4/CD8 antibody provided herein; and enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD4-expressing cells and/or CD8-expressing cells based on binding of the CD4-expressing cells and/or CD8-expressing cells to the multispecific CD4/CD8 antibody. In some embodiments, the CD4-expressing cells and/or CD8-expressing cells is a T cell. In some embodiments, the CD4-expressing cells and/or CD8-expressing cells is a CD4+ T helper cell. In some embodiments, the CD4-expressing cells and/or CD8-expressing cells is provided as a sample comprising a population of cells. In some embodiments, the cells are lymphocytes. In some embodiments, the cells are T cells. In some embodiments, the sample is a blood sample. In some embodiments, the sample is a tissue sample. In some embodiments, the multispecific CD4/CD8 antibody is a multispecific CD4/CD8 antibody provided herein. In some embodiments, the cells comprise CD4-expressing cells. In some embodiments, the cells comprise CD8-expressing cells. In some embodiments, the cells comprise CD4-expressing cells and CD8-expressing cells.







DETAILED DESCRIPTION

Various publications, articles and patents are cited or described in the background and throughout the specification; each of these references is herein incorporated by reference in its entirety. Discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is for the purpose of providing context for the invention. Such discussion is not an admission that any or all of these matters form part of the prior art with respect to any inventions disclosed or claimed.


Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which this invention pertains. Otherwise, certain terms used herein have the meanings as set forth in the specification.


It must be noted that as used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural reference unless the context clearly dictates otherwise.


Unless otherwise stated, any numerical values, such as a concentration or a concentration range described herein, are to be understood as being modified in all instances by the term “about.” Thus, a numerical value typically includes ±10% of the recited value. For example, a concentration of 1 mg/mL includes 0.9 mg/mL to 1.1 mg/mL. Likewise, a concentration range of 1% to 10% (w/v) includes 0.9% (w/v) to 11% (w/v). As used herein, the use of a numerical range expressly includes all possible subranges, all individual numerical values within that range, including integers within such ranges and fractions of the values unless the context clearly indicates otherwise.


Unless otherwise indicated, the term “at least” preceding a series of elements is to be understood to refer to every element in the series.


Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments described herein. Such equivalents are intended to been compassed by the invention.


As used herein, the terms “comprises,” “comprising,” “includes,” “including,” “has,” “having,” “contains” or “containing,” or any other variation thereof, will be understood to imply the inclusion of a stated integer or group of integers but not the exclusion of any other integer or group of integers and are intended to be non-exclusive or open-ended. For example, a composition, a mixture, a process, a method, an article, or an apparatus that comprises a list of elements is not necessarily limited to only those elements but can include other elements not expressly listed or inherent to such composition, mixture, process, method, article, or apparatus. Further, unless expressly stated to the contrary, “or” refers to an inclusive or and not to an exclusive or. For example, a condition A or B is satisfied by any one of the following: A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B are true (or present).


As used herein, the conjunctive term “and/or” between multiple recited elements is understood as encompassing both individual and combined options. For instance, where two elements are conjoined by “and/or,” a first option refers to the applicability of the first element without the second. A second option refers to the applicability of the second element without the first. A third option refers to the applicability of the first and second elements together. Any one of these options is understood to fall within the meaning, and therefore satisfy the requirement of the term “and/or” as used herein. Concurrent applicability of more than one of the options is also understood to fall within the meaning, and therefore satisfy the requirement of the term “and/or.”


As used herein, the term “consists of,” or variations such as “consist of” or “consisting of,” as used throughout the specification and claims, indicate the inclusion of any recited integer or group of integers, but that no additional integer or group of integers can be added to the specified method, structure, or composition.


As used herein, the term “consists essentially of,” or variations such as “consist essentially of” or “consisting essentially of,” as used throughout the specification and claims, indicate the inclusion of any recited integer or group of integers, and the optional inclusion of any recited integer or group of integers that do not materially change the basic or novel properties of the specified method, structure or composition. See M.P.E.P. § 2111.03.


As used herein, “subject” means any animal, preferably a mammal, most preferably a human. The term “mammal” as used herein, encompasses any mammal. Examples of mammals include, but are not limited to, cows, horses, sheep, pigs, cats, dogs, mice, rats, rabbits, guinea pigs, monkeys, humans, etc. In a specific embodiments, the subject is a human.


It should also be understood that the terms “about,” “approximately,” “generally,” “substantially,” and like terms, used herein when referring to a dimension or characteristic of a component of embodiments provided herein, indicate that the described dimension/characteristic is not a strict boundary or parameter and does not exclude minor variations therefrom that are functionally the same or similar, as would be understood by one having ordinary skill in the art. At a minimum, such references that include a numerical parameter would include variations that, using mathematical and industrial principles accepted in the art (e.g., rounding, measurement or other systematic errors, manufacturing tolerances, etc.), would not vary the least significant digit.


The terms “identical” or percent “identity,” in the context of two or more nucleic acids or polypeptide sequences (e.g., CD8 antibody and polynucleotides that encode them, CD4 antibody and polynucleotides that encode them, multispecific CD4/CD8 antibodies and polynucleotides that encode them), refer to two or more sequences or subsequences that are the same or have a specified percentage of amino acid residues or nucleotides that are the same, when compared and aligned for maximum correspondence, as measured using one of the following sequence comparison algorithms or by visual inspection.


For sequence comparison, typically one sequence acts as a reference sequence, to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are input into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. The sequence comparison algorithm then calculates the percent sequence identity for the test sequence(s) relative to the reference sequence, based on the designated program parameters.


Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith & Waterman, Adv. Appl. Math. 2:482 (1981), by the homology alignment algorithm of Needleman & Wunsch, J. Mol. Biol. 48:443 (1970), by the search for similarity method of Pearson & Lipman, Proc. Nat'l. Acad. Sci. USA 85:2444 (1988), by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, WI), or by visual inspection (see generally, Current Protocols in Molecular Biology, F. M. Ausubel et al., eds., Current Protocols, a joint venture between Greene Publishing Associates, Inc. and John Wiley & Sons, Inc., (1995 Supplement) (Ausubel)).


Examples of algorithms that are suitable for determining percent sequence identity and sequence similarity are the BLAST and BLAST 2.0 algorithms, which are described in Altschul et al. (1990) J. Mol. Biol. 215: 403-410 and Altschul et al. (1997) Nucleic Acids Res. 25: 3389-3402, respectively. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information. This algorithm involves first identifying high scoring sequence pairs (HSPs) by identifying short words of length W in the query sequence, which either match or satisfy some positive-valued threshold score T when aligned with a word of the same length in a database sequence. T is referred to as the neighborhood word score threshold (Altschul et al., supra). These initial neighborhood word hits act as seeds for initiating searches to find longer HSPs containing them. The word hits are then extended in both directions along each sequence for as far as the cumulative alignment score can be increased.


Cumulative scores are calculated using, for nucleotide sequences, the parameters M (reward score for a pair of matching residues; always >0) and N (penalty score for mismatching residues; always <0). For amino acid sequences, a scoring matrix is used to calculate the cumulative score. Extension of the word hits in each direction are halted when: the cumulative alignment score falls off by the quantity X from its maximum achieved value; the cumulative score goes to zero or below, due to the accumulation of one or more negative-scoring residue alignments; or the end of either sequence is reached. The BLAST algorithm parameters W, T, and X determine the sensitivity and speed of the alignment. The BLASTN program (for nucleotide sequences) uses as defaults a word length (W) of 11, an expectation (E) of 10, M=5, N=−4, and a comparison of both strands. For amino acid sequences, the BLASTP program uses as defaults a word length (W) of 3, an expectation (E) of 10, and the BLOSUM62 scoring matrix (see Henikoff & Henikoff, Proc. Natl. Acad. Sci. USA 89:10915 (1989)).


In addition to calculating percent sequence identity, the BLAST algorithm also performs a statistical analysis of the similarity between two sequences (see, e.g., Karlin & Altschul, Proc. Nat'l. Acad. Sci. USA 90:5873-5787 (1993)). One measure of similarity provided by the BLAST algorithm is the smallest sum probability (P(N)), which provides an indication of the probability by which a match between two nucleotide or amino acid sequences would occur by chance. For example, a nucleic acid is considered similar to a reference sequence if the smallest sum probability in a comparison of the test nucleic acid to the reference nucleic acid is less than about 0.1, more preferably less than about 0.01, and most preferably less than about 0.001.


A further indication that two nucleic acid sequences or polypeptides are substantially identical is that the polypeptide encoded by the first nucleic acid is immunologically cross reactive with the polypeptide encoded by the second nucleic acid, as described below. Thus, a polypeptide is typically substantially identical to a second polypeptide, for example, where the two peptides differ only by conservative substitutions. Another indication that two nucleic acid sequences are substantially identical is that the two molecules hybridize to each other under stringent conditions.


As used herein, the term “polynucleotide,” synonymously referred to as “nucleic acid molecule,” “nucleotides” or “nucleic acids,” refers to any polyribonucleotide or polydeoxyribonucleotide, which can be unmodified RNA or DNA or modified RNA or DNA. “Polynucleotides” include, without limitation single- and double-stranded DNA, DNA that is a mixture of single- and double-stranded regions, single- and double-stranded RNA, and RNA that is mixture of single- and double-stranded regions, hybrid molecules comprising DNA and RNA that can be single-stranded or, more typically, double-stranded or a mixture of single- and double-stranded regions. In addition, “polynucleotide” refers to triple-stranded regions comprising RNA or DNA or both RNA and DNA. The term polynucleotide also includes DNAs or RNAs containing one or more modified bases and DNAs or RNAs with backbones modified for stability or for other reasons. “Modified” bases include, for example, tritylated bases and unusual bases such as inosine. A variety of modifications can be made to DNA and RNA; thus, “polynucleotide” embraces chemically, enzymatically or metabolically modified forms of polynucleotides as typically found in nature, as well as the chemical forms of DNA and RNA characteristic of viruses and cells. “Polynucleotide” also embraces relatively short nucleic acid chains, often referred to as oligonucleotides.


As used herein, the term “vector” is a replicon in which another nucleic acid segment can be operably inserted so as to bring about the replication or expression of the segment.


As used herein, the term “host cell” refers to a cell comprising a nucleic acid molecule provided herein. The “host cell” can be any type of cell, e.g., a primary cell, a cell in culture, or a cell from a cell line. In one embodiment, a “host cell” is a cell transfected with a nucleic acid molecule provided herein. In another embodiment, a “host cell” is a progeny or potential progeny of such a transfected cell. A progeny of a cell may or may not be identical to the parent cell, e.g., due to mutations or environmental influences that can occur in succeeding generations or integration of the nucleic acid molecule into the host cell genome.


The term “expression” as used herein, refers to the biosynthesis of a gene product. The term encompasses the transcription of a gene into RNA. The term also encompasses translation of RNA into one or more polypeptides, and further encompasses all naturally occurring post-transcriptional and post-translational modifications. The expressed antibody can be within the cytoplasm of a host cell, into the extracellular milieu such as the growth medium of a cell culture or anchored to the cell membrane.


As used herein, the terms “peptide,” “polypeptide,” or “protein” can refer to a molecule comprised of amino acids and can be recognized as a protein by those of skill in the art. The conventional one-letter or three-letter code for amino acid residues is used herein. The terms “peptide,” “polypeptide,” and “protein” can be used interchangeably herein to refer to polymers of amino acids of any length. The polymer can be linear or branched, it can comprise modified amino acids, and it can be interrupted by non-amino acids. The terms also encompass an amino acid polymer that has been modified naturally or by intervention; for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation or modification, such as conjugation with a labeling component. Also included within the definition are, for example, polypeptides containing one or more analogs of an amino acid (including, for example, unnatural amino acids, etc.), as well as other modifications known in the art.


The peptide sequences described herein are written according to the usual convention whereby the N-terminal region of the peptide is on the left and the C-terminal region is on the right. Although isomeric forms of the amino acids are known, it is the L-form of the amino acid that is represented unless otherwise expressly indicated.


Antibodies


Provided herein are CD8 antibodies or antigen-binding fragments thereof, nucleic acids and expression vectors encoding the antibodies, recombinant cells containing the vectors, and compositions comprising the antibodies. Methods of making the antibodies, and methods of using the antibodies to treat diseases are also provided. The antibodies disclosed herein possess one or more desirable functional properties, including but not limited to high-affinity binding to CD8 or high specificity to CD8. In certain embodiments, the antibodies disclosed herein possess the ability to treat or prevent a disease or disorder when administered to a subject alone or in combination with other therapies.


Also provided herein are CD8 multispecific antibodies or antigen-binding fragments thereof, nucleic acids and expression vectors encoding the multispecific antibodies, recombinant cells containing the vectors, and compositions comprising the multispecific antibodies. Methods of making the antibodies, and methods of using the multispecific antibodies to treat diseases, including cancer, are also provided. The antibodies disclosed herein possess one or more desirable functional properties. In some embodiments, the multispecific antibodies provided herein have high-affinity binding to CD8. In some embodiments, the multispecific antibodies provided herein have high-affinity binding to a second target antigen. In some embodiments, the multispecific antibodies provided herein have high specificity to CD8. In some embodiments, the multispecific antibodies provided herein have high specificity to a second target antigen. In some embodiments, the multispecific antibodies provided herein have the ability to treat or prevent a disease or disorder when administered alone. In some embodiments, the multispecific antibodies provided herein have the ability to treat or prevent a disease or disorder when administered in combination with other therapies. In certain embodiments, the multispecific antibody is a bispecific antibody. In some embodiments, the multispecific antibody is a trispecific antibody. In some embodiments, the multispecific antibody is a quadraspecific antibody. In certain embodiments, the second target is CD4.


Also provided herein are CD4 antibodies or antigen-binding fragments thereof, nucleic acids and expression vectors encoding the antibodies, recombinant cells containing the vectors, and compositions comprising the antibodies. Methods of making the antibodies, and methods of using the antibodies to treat diseases are also provided. The antibodies disclosed herein possess one or more desirable functional properties, including but not limited to high-affinity binding to CD4 or high specificity to CD4. In certain embodiments, the antibodies disclosed herein possess the ability to treat or prevent a disease or disorder when administered to a subject alone or in combination with other therapies.


Also provided herein are CD4 multispecific antibodies or antigen-binding fragments thereof, nucleic acids and expression vectors encoding the multispecific antibodies, recombinant cells containing the vectors, and compositions comprising the multispecific antibodies. Methods of making the antibodies, and methods of using the multispecific antibodies to treat diseases, including cancer, are also provided. The antibodies disclosed herein possess one or more desirable functional properties. In some embodiments, the multispecific antibodies provided herein have high-affinity binding to CD4. In some embodiments, the multispecific antibodies provided herein have high-affinity binding to a second target antigen. In some embodiments, the multispecific antibodies provided herein have high specificity to CD4. In some embodiments, the multispecific antibodies provided herein have high specificity to a second target antigen. In some embodiments, the multispecific antibodies provided herein have the ability to treat or prevent a disease or disorder when administered alone. In some embodiments, the multispecific antibodies provided herein have the ability to treat or prevent a disease or disorder when administered in combination with other therapies. In certain embodiments, the multispecific antibody is a bispecific antibody. In some embodiments, the multispecific antibody is a trispecific antibody. In some embodiments, the multispecific antibody is a quadraspecific antibody. In certain embodiments, the second target is CD8.


As used herein, the term “antibody” is used in a broad sense and includes immunoglobulin or antibody molecules including human, humanized, composite and chimeric antibodies and antibody fragments that are monoclonal or polyclonal. In general, antibodies are proteins or peptide chains that exhibit binding specificity to a specific antigen. Antibody structures are well known. Immunoglobulins can be assigned to five major classes (i.e., IgA, IgD, IgE, IgG and IgM), depending on the heavy chain constant domain amino acid sequence. IgA and IgG are further sub-classified as the isotypes IgA1, IgA2, IgG1, IgG2, IgG3 and IgG4. Accordingly, the antibodies provided herein can be of any of the five major classes or corresponding sub-classes. In specific embodiments, the antibodies provided herein are IgG1, IgG2, IgG3 or IgG4. Antibody light chains of vertebrate species can be assigned to one of two clearly distinct types, namely kappa and lambda, based on the amino acid sequences of their constant domains. Accordingly, the antibodies provided herein can, in certain embodiments, contain a kappa light chain constant domain. The antibodies provided herein can, in certain embodiments, also contain a lambda light chain constant domain. According to particular embodiments, the antibodies provided herein include heavy and/or light chain constant regions from rat or human antibodies. In specific embodiments, the constant region is a human constant region.


In addition to the heavy and light constant domains, antibodies contain an antigen-binding region that is made up of a light chain variable region (VL) and a heavy chain variable region (VH), each of which contains three domains (i.e., complementarity determining regions 1 (CDR1), CDR2 and CDR3. A “CDR” refers to one of three hypervariable regions (HCDR1, HCDR2 or HCDR3) within the non-framework region of the immunoglobulin (Ig or antibody) VH β-sheet framework, or one of three hypervariable regions (LCDR1, LCDR2 or LCDR3) within the non-framework region of the antibody VL 3-sheet framework. Accordingly, CDRs are variable region sequences interspersed within the framework region sequences. CDR regions are well known to those skilled in the art and have been defined by, for example, Kabat as the regions of most hypervariability within the antibody variable (V) domains (Kabat et al., J. Biol. Chem. 252:6609-6616 (1977); Kabat, Adv. Prot. Chem. 32:1-75 (1978)). CDR region sequences also have been defined structurally by Chothia as those residues that are not part of the conserved β-sheet framework, and thus are able to adapt different conformations (Chothia and Lesk, J. Mol. Biol. 196:901-917 (1987)). Both terminologies are well recognized in the art. CDR region sequences have also been defined by AbM, Contact and IMGT. Exemplary CDR region sequences are illustrated herein, for example, in the tables provided in the Examples below. The positions of CDRs within a canonical antibody variable region have been determined by comparison of numerous structures (Al-Lazikani et al., J. Mol. Biol. 273:927-948 (1997); Morea et al., Methods 20:267-279 (2000)). Because the number of residues within a hypervariable region varies in different antibodies, additional residues relative to the canonical positions are conventionally numbered with a, b, c and so forth next to the residue number in the canonical variable region numbering scheme (Al-Lazikani et al., supra (1997)). Such nomenclature is similarly well known to those skilled in the art.


The light chain variable region CDR1 domain is interchangeably referred to herein as LCDR1 or VL CDR1. The light chain variable region CDR2 domain is interchangeably referred to herein as LCDR2 or VL CDR2. The light chain variable region CDR3 domain is interchangeably referred to herein as LCDR3 or VL CDR3. The heavy chain variable region CDR1 domain is interchangeably referred to herein as HCDR1 or VH CDR1. The heavy chain variable region CDR2 domain is interchangeably referred to herein as HCDR2 or VH CDR2. The heavy chain variable region CDR1 domain is interchangeably referred to herein as HCDR3 or VH CDR3.


The term “hypervariable region”, such as a VH or VL, when used herein refers to the regions of an antibody variable region that are hypervariable in sequence and/or form structurally defined loops. Generally, antibodies comprise six hypervariable regions; three in the VH (HCDR1, HCDR2, HCDR3), and three in the VL (LCDR1, LCDR2, LCDR3). A number of hypervariable region delineations are in use and are encompassed herein. The “Kabat” CDRs are based on sequence variability and are the most commonly used (see, e.g., Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD (1991)). “Chothia” refers instead to the location of the structural loops (see, e.g., Chothia and Lesk, J. Mol. Biol. 196:901-917 (1987)). The end of the Chothia CDR-HCDR1 loop when numbered using the Kabat numbering convention varies between H32 and H34 depending on the length of the loop (this is because the Kabat numbering scheme places the insertions at H35A and H35B; if neither 35A nor 35B is present, the loop ends at 32; if only 35A is present, the loop ends at 33; if both 35A and 35B are present, the loop ends at 34). The “AbM” hypervariable regions represent a compromise between the Kabat CDRs and Chothia structural loops, and are used by Oxford Molecular's AbM antibody modeling software (see, e.g., Martin, in Antibody Engineering, Vol. 2, Chapter 3, Springer Verlag). “Contact” hypervariable regions are based on an analysis of the available complex crystal structures.


Recently, a universal numbering system has been developed and widely adopted, ImMunoGeneTics (IMGT) Information System® (Lafranc et al., Dev. Comp. Immunol. 27(1):55-77 (2003)). IMGT is an integrated information system specializing in immunoglobulins (IG), T cell receptors (TR) and major histocompatibility complex (MHC) of human and other vertebrates. Herein, the CDRs are referred to in terms of both the amino acid sequence and the location within the light or heavy chain. As the “location” of the CDRs within the structure of the immunoglobulin variable domain is conserved between species and present in structures called loops, by using numbering systems that align variable domain sequences according to structural features, CDR and framework residues and are readily identified. This information can be used in grafting and replacement of CDR residues from immunoglobulins of one species into an acceptor framework from, typically, a human antibody. An additional numbering system (AHon) has been developed by Honegger and Pluckthun, J. Mol. Biol. 309: 657-670 (2001). Correspondence between the numbering system, including, for example, the Kabat numbering and the IMGT unique numbering system, is well known to one skilled in the art (see, e.g., Kabat, supra; Chothia and Lesk, supra; Martin, supra; Lefranc et al., supra). An Exemplary system, shown herein, combines Kabat and Chothia.



















Exemplary
IMGT
Kabat
AbM
Chothia
Contact







VH CDR1
26-35
27-38
31-35
26-35
26-32
30-35


VH CDR2
50-65
56-65
50-65
50-58
53-55
47-58


VH CDR3
 95-102
105-117
 95-102
 95-102
 96-101
 93-101


VL CDR1
24-34
27-38
24-34
24-34
26-32
30-36


VL CDR2
50-56
56-65
50-56
50-56
50-52
46-55


VL CDR3
89-97
105-117
89-97
89-97
91-96
89-96









Hypervariable regions may comprise “extended hypervariable regions” as follows: 24-36 or 24-34 (LCDR1), 46-56 or 50-56 (LCDR2) and 89-97 or 89-96 (LCDR3) in the VL and 26-35 or 26-35A (HCDR1), 50-65 or 49-65 (HCDR2) and 93-102, 94-102, or 95-102 (HCDR3) in the VH. CDR sequences, reflecting each of the above numbering schemes, are provided herein, including in tables of the Examples below.


The term “constant region” or “constant domain” refers to a carboxy terminal portion of the light and heavy chain which is not directly involved in binding of the antibody to antigen but exhibits various effector function, such as interaction with the Fc receptor. The terms refer to the portion of an immunoglobulin molecule having a more conserved amino acid sequence relative to the other portion of the immunoglobulin, the variable region, which contains the antigen binding site. The constant region may contain the CH1, CH2 and CH3 regions of the heavy chain and the CL region of the light chain.


The term “framework” or “FR” residues are those variable region residues flanking the CDRs. FR residues are present, for example, in chimeric, humanized, human, domain antibodies, diabodies, linear antibodies, and bispecific antibodies. FR residues are those variable domain residues other than the hypervariable region residues or CDR residues.


As used herein, the term an “isolated antibody” refers to an antibody which is substantially free of other antibodies having different antigenic specificities (e.g., an isolated antibody that specifically binds to CD8 is substantially free of antibodies that do not bind to CD8; an isolated antibody that specifically binds to CD4 is substantially free of antibodies that do not bind to CD4). In addition, an isolated antibody is substantially free of other cellular material and/or chemicals.


As used herein, the term “monoclonal antibody” refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations that can be present in minor amounts. Monoclonal antibodies provided herein can be made by the hybridoma method, phage display technology, single lymphocyte gene cloning technology, or by recombinant DNA methods. For example, the monoclonal antibodies can be produced by a hybridoma which includes a B cell obtained from a transgenic nonhuman animal, such as a transgenic mouse or rat, having a genome comprising a human heavy chain transgene and a light chain transgene.


As used herein, the term “antigen-binding fragment” refers to an antibody fragment such as, for example, a diabody, a Fab, a Fab′, a F(ab′)2, an Fv fragment, a disulfide stabilized Fv fragment (dsFv), a (dsFv)2, a bispecific dsFv (dsFv-dsFv′), a disulfide stabilized diabody (ds diabody), a single-chain antibody molecule (scFv), a single domain antibody (sdAb) an scFv dimer (bivalent diabody), a multispecific antibody formed from a portion of an antibody comprising one or more CDRs, a camelized single domain antibody, a nanobody, a domain antibody, a bivalent domain antibody, or any other antibody fragment that binds to an antigen but does not comprise a complete antibody structure. An antigen-binding fragment is capable of binding to the same antigen to which the parent antibody or a parent antibody fragment binds. According to particular embodiments, the antigen-binding fragment comprises a light chain variable region, a light chain constant region, and an Fd segment of the heavy chain. According to other particular embodiments, the antigen-binding fragment comprises Fab and F(ab′).


As used herein, the term “single-chain antibody” refers to a conventional single-chain antibody in the field, which comprises a heavy chain variable region and a light chain variable region connected by a short peptide of about 15 to about 20 amino acids. As used herein, the term “single domain antibody” refers to a conventional single domain antibody in the field, which comprises a heavy chain variable region and a heavy chain constant region or which comprises only a heavy chain variable region.


As used herein, the term “human antibody” refers to an antibody produced by a human or an antibody having an amino acid sequence corresponding to an antibody produced by a human made using any technique known in the art. This definition of a human antibody includes intact or full-length antibodies, fragments thereof, and/or antibodies comprising at least one human heavy and/or light chain polypeptide.


As used herein, the term “humanized antibody” refers to a non-human antibody that is modified to increase the sequence homology to that of a human antibody, such that the antigen-binding properties of the antibody are retained, but its antigenicity in the human body is reduced.


As used herein, the term “chimeric antibody” refers to an antibody wherein the amino acid sequence of the immunoglobulin molecule is derived from two or more species. The variable region of both the light and heavy chains often corresponds to the variable region of an antibody derived from one species of mammal (e.g., mouse, rat, rabbit, etc.) having the desired specificity, affinity, and capability, while the constant regions correspond to the sequences of an antibody derived from another species of mammal (e.g., human) to avoid eliciting an immune response in that species.


As used herein, the term “multispecific antibody” refers to an antibody that comprises a plurality of immunoglobulin variable domain sequences, wherein a first immunoglobulin variable domain sequence of the plurality has binding specificity for a first epitope and a second immunoglobulin variable domain sequence of the plurality has binding specificity for a second epitope. In an embodiment, the first and second epitopes do not overlap or do not substantially overlap. In an embodiment, the first and second epitopes are on different antigens, e.g., the different proteins (or different subunits of a multimeric protein). In an embodiment, a multispecific antibody comprises a third, fourth, or fifth immunoglobulin variable domain. In an embodiment, a multispecific antibody is a bispecific antibody molecule, a trispecific antibody molecule, or a tetraspecific antibody molecule.


As used herein, the term “bispecific antibody” refers to a multispecific antibody that binds no more than two epitopes or two antigens. A bispecific antibody is characterized by a first immunoglobulin variable domain sequence which has binding specificity for a first epitope (e.g., an epitope on a target antigen) and a second immunoglobulin variable domain sequence that has binding specificity for a second epitope. In an embodiment, the first and second epitopes are on different antigens, e.g., the different proteins (or different subunits of a multimeric protein). In an embodiment, a bispecific antibody comprises a heavy chain variable domain sequence and a light chain variable domain sequence which have binding specificity for a first epitope and a heavy chain variable domain sequence and a light chain variable domain sequence which have binding specificity for a second epitope. In an embodiment, a bispecific antibody comprises a half antibody, or fragment thereof, having binding specificity for a first epitope and a half antibody, or fragment thereof, having binding specificity for a second epitope. In an embodiment, a bispecific antibody comprises a scFv, or fragment thereof, having binding specificity for a first epitope, and a scFv, or fragment thereof, having binding specificity for a second epitope. A “trispecific antibody” is a multispecific antibody that binds three distinct antigens, or three distinct epitopes within the same antigen. A “quadraspecific antibody” is a multispecific antibody that binds four distinct antigens, or four distinct epitopes within the same antigen.


As used herein, the term “CD4” refers to a polypeptide capable of forming a co-receptor with the T cell receptor (TCR) when expressed on the surface of T cells. The term “CD4” includes any CD4 variant, isoform, and species homolog, which is naturally expressed by cells (including T cells) or can be expressed on cells transfected with genes or cDNA encoding the polypeptide. In specific embodiments, the CD4 is a human CD4. An exemplary human CD4 amino acid sequence is provided by GenBank Accession Number NP_000607.1.


As used herein, the term “CD8” refers to a polypeptide capable of forming a co-receptor with the T cell receptor (TCR) when expressed on the surface of T cells. The term “CD8” includes any CD8 variant, isoform, and species homolog, which is naturally expressed by cells (including T cells) or can be expressed on cells transfected with genes or cDNA encoding the polypeptide. In specific embodiments, the CD8 is a human CD8. CD8 can comprise a CD8α chain or a CD8β chain. In certain embodiments, the CD8 comprises a CD8αβ heterodimer. In certain embodiments, CD8 comprises a CD8αα homodimer. In certain embodiments, CD8 comprises a CD8ββ homodimer. An exemplary human CD8α amino acid sequence is provided by GenBank Accession Number AAH25715. An exemplary human CD8β amino acid sequence is provided by GenBank Accession Number AAI00912.


As used herein, an antibody that “specifically binds to CD8” refers to an antibody that binds to a CD8, preferably a human CD8, with a KD of 1×10−7 M or less, such as 1×10−8 M or less, 5×10−9 M or less, 1×10−9 M or less, 5×10−10 M or less, or 1×10−10 M or less. As used herein, an antibody that “specifically binds to CD4” refers to an antibody that binds to a CD4, preferably a human CD4, with a KD of 1×10−7 M or less, such as 1×10−8 M or less, 5×10−9 M or less, 1×10−9 M or less, 5×10−10 M or less, or 1×10−10 M or less. As used herein, an antibody that “specifically binds to a second target antigen” refers to an antibody that binds to a second target antigen with a KD of 1×10−7 M or less, such as 1×10−8 M or less, 5×10−9 M or less, 1×10−9 M or less, 5×10−10 M or less, or 1×10−10 M or less. As used herein, an antibody that “specifically binds to a third target antigen” refers to an antibody that binds to a third target antigen with a KD of 1×10−7 M or less, such as 1×10−8 M or less, 5×10−9 M or less, 1×10−9 M or less, 5×10−10 M or less, or 1×10−10 M or less. As used herein, an antibody that “specifically binds to a fourth target antigen” refers to an antibody that binds to a fourth target antigen with a KD of 1×10−7 M or less, such as 1×10−8 M or less, 5×10−9 M or less, 1×10−9 M or less, 5×10−10 M or less, or 1×10−10 M or less.


The term “KD” refers to the dissociation constant, which is obtained from the ratio of Kd to Ka (i.e., Kd/Ka) and is expressed as a molar concentration (M). KD values for antibodies can be determined using methods in the art in view of the present disclosure. For example, the KD of an antibody can be determined by using surface plasmon resonance, such as by using a biosensor system, e.g., a Biacore® system, or by using bio-layer interferometry technology, such as an Octet® RED96 (interferometry instrument) system. The smaller the value of the KD of an antibody, the higher affinity that the antibody binds to a target antigen.


In one aspect, provided herein is an antibody that binds to CD8. In some embodiments, the CD8 antibody binds CD8α. In some embodiments, the CD8 antibody binds CD8β. In some embodiments, the CD8 antibody binds at the interface of CD8α and CD8β. In some embodiments, provided herein is an antibody that binds to a CD8 antigen. In some embodiments, the CD8 antibody binds CD8α antigen. In some embodiments, the CD8 antibody binds CD8β antigen. In some embodiments, the CD8 antibody binds an antigen on the interface of CD8α and CD8β. In some embodiments, provided herein is an antibody that binds to a CD8 epitope. In some embodiments, the CD8 antibody binds CD8α epitope. In some embodiments, the CD8 antibody binds CD8β epitope. In some embodiments, the CD8 antibody binds an epitope at the interface of CD8α and CD8β.


In some embodiments, the antibody comprises a heavy chain variable region and a light chain variable region. In a some embodiments, the CD8 antibody is not a single domain antibody or nanobody. In some embodiments, the CD8 antibody is a humanized antibody. In some embodiments, the CD8 antibody is a fully human antibody.


In certain embodiments, provided herein is a CD8 antibody comprising a VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and/or VL CDR3 of any one of the antibodies described herein. In some embodiments, provided herein is a CD8 antibody comprising a VH region of any one of the antibodies described herein. In some embodiments, provided herein is a CD8 antibody comprising a VL region of any one of the antibodies described herein. In some embodiments, provided herein is a CD8 antibody comprising a VH region of any one of the antibodies described herein, and a VL region of any one of the antibodies described herein. In some embodiments, provided herein is a CD8 antibody comprising a VH CDR1, VH CDR2, and VH CDR3 of any one of the antibodies described herein. In some embodiments, provided herein is a CD8 antibody comprising a VL CDR1, VL CDR2, and VL CDR3 of any one of the antibodies described herein. In some embodiments, provided herein is a CD8 antibody comprising a VH CDR1, VH CDR2, and VH CDR3 of any one of the antibodies described herein; and a VL CDR1, VL CDR2, and VL CDR3 of any one of the antibodies described herein. Representative VH and VL amino acid sequences, including VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 amino acid sequences, of CD8 antibodies provided herein are provided in Tables 2-7.


In certain embodiments, provided herein is a CD8 multispecific antibody comprising a binding domain that binds to CD8 having a VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and/or VL CDR3 of any one of the antibodies described herein. In some embodiments, provided herein is a CD8 multispecific antibody comprising a binding domain that binds to CD8 having a VH region of any one of the antibodies described herein. In some embodiments, provided herein is a CD8 multispecific antibody comprising a binding domain that binds to CD8 having a VL region of any one of the antibodies described herein. In some embodiments, provided herein is a CD8 multispecific antibody comprising a binding domain that binds to CD8 having a VH region of any one of the antibodies described herein, and a VL region of any one of the antibodies described herein. In some embodiments, provided herein is a CD8 multispecific antibody comprising a binding domain that binds to CD8 having a VH CDR1, VH CDR2, and VH CDR3 of any one of the antibodies described. In some embodiments, provided herein is a CD8 multispecific antibody comprising a binding domain that binds to CD8 having a VL CDR1, VL CDR2, and VL CDR3 of any one of the antibodies described herein. In some embodiments, provided herein is a CD8 multispecific antibody comprising a binding domain that binds to CD8 having a VH CDR1, VH CDR2, and VH CDR3 of any one of the antibodies described herein; and a VL CDR1, VL CDR2, and VL CDR3 of any one of the antibodies described herein. In certain embodiments, the CD8 antibody is a bispecific antibody. In certain embodiments, the CD8 antibody is a trispecific antibody. In certain embodiments, the CD8 antibody is a quadraspecific antibody.


In some embodiments, the antibody specifically binds CD8. In other embodiments, the CD8 is present on the surface of a T cell.


In some embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In other embodiments, the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody. In some embodiments, the antibody is a bispecific antibody. In some embodiments, the antibody is a trispecific antibody. In some embodiments, the antibody is a quadraspecific antibody. In certain embodiments, the antibody is multivalent. In other embodiments, the antibody is capable of binding at least three antigens. In some embodiments, the antibody is capable of binding at least four antigens. In some embodiments, the antibody is capable of binding at least five antigens.


In certain embodiments, provided is a CD8 antibody that is an intact antibody. In other embodiments, provided is a CD8 antibody is an antigen binding fragment of the CD8 antibody. In some embodiments, the antigen binding fragment of the CD8 antibody is a functional fragment.


In some embodiments, the antigen binding fragment is a diabody. In some embodiments, the antigen binding fragment is a Fab. In some embodiments, the antigen binding fragment is a Fab′. In some embodiments, the antigen binding fragment is a F(ab′)2. In some embodiments, the antigen binding fragment is a Fv fragment. In some embodiments, the antigen binding fragment is a disulfide stabilized Fv fragment (dsFv). In some embodiments, the antigen binding fragment is a (dsFv)2. In some embodiments, the antigen binding fragment is a bispecific dsFv (dsFv-dsFv′). In some embodiments, the antigen binding fragment is a disulfide stabilized diabody (ds diabody). In some embodiments, the antigen binding fragment is a single-chain antibody molecule (scFv). In some embodiments, the antigen binding fragment is a single domain antibody (sdAb). In some embodiments, the antigen binding fragment is an scFv dimer (bivalent diabody). In some embodiments, the antigen binding fragment is a multispecific antibody formed from a portion of an antibody comprising one or more CDRs. In some embodiments, the antigen binding fragment is a camelized single domain antibody. In some embodiments, the antigen binding fragment is a nanobody. In some embodiments, the antigen binding fragment is a domain antibody. In some embodiments, the antigen binding fragment is a bivalent domain antibody. In some embodiments, the antigen binding fragment is an antibody fragment that binds to an antigen but does not comprise a complete antibody structure.


In specific embodiments, the CD8 antibody comprises a VH region and a VL region. In some embodiments, the CD8 antibody is a single chain antibody. In some embodiments, the CD8 antibody is a single domain antibody. In some embodiments, the CD8 antibody is a nanobody. In certain embodiments, the CD8 antibody is a VHH antibody. In certain embodiments, the CD8 antibody is a llama antibody. In some embodiments, the CD8 antibody is not a single chain antibody. In some embodiments, the CD8 antibody is not a single domain antibody. In some embodiments, the CD8 antibody is not a nanobody. In certain embodiments, the CD8 antibody is not a VHH antibody. In certain embodiments, the CD8 antibody is not a llama antibody. In some embodiments, the CD8 antibody is a multispecific antibody. In other embodiments, the CD8 antibody is a bispecific antibody. In other embodiments, the CD8 antibody is a trispecific antibody. In other embodiments, the CD8 antibody is a quadraspecific antibody. In certain embodiments, the multispecific antibody comprises an antigen binding fragment of a CD8 antibody provided herein. In other embodiments, the bispecific antibody comprises an antigen binding fragment of a CD8 antibody provided herein. In other embodiments, the trispecific antibody comprises an antigen binding fragment of a CD8 antibody provided herein. In other embodiments, the quadraspecific antibody comprises an antigen binding fragment of a CD8 antibody provided herein. In some embodiments, the CD8 antibody is an agonistic antibody. In certain embodiments, the CD8 antibody activates T cells. In other embodiments, the CD8 antibody is an antagonistic antibody. In certain embodiments, the CD8 antibody inactivates T cells. In some embodiments, the CD8 antibody blocks activation of T cells. In some embodiments, the CD8 antibody modulates the activity of T cells. In some embodiments, the CD8 antibody neither activates or inactivates the activity of T cells. In specific embodiments, the T cells are human T cells.


In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences are according to the Kabat numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences are according to the Chothia numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences are according to the Exemplary numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences are according to the Contact numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences are according to the IMGT numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences are according to the AbM numbering system. Exemplary sets of 6 CDRs (VH CDR1-3 and VL CDR1-3) of certain antibody embodiments are provided herein. Other sets of CDRs are contemplated and within the scope of the antibody embodiments provided herein.


In one aspect, provided herein is an antibody that binds CD8. In one embodiment, provided is an antibody having a VH CDR1, VH CDR2 and a VH CDR3 of a CD8 antibody provided herein. In one embodiment, provided is an antibody having a VL CDR1, VL CDR2 and a VL CDR3 of a CD8 antibody provided herein. In one embodiment, provided is an antibody having a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of a CD8 antibody provided herein. In one embodiment, provided is an antibody having a VH of a CD8 antibody provided herein. In one embodiment, provided is an antibody having a VL of a CD8 antibody provided herein. In one embodiment, provided is an antibody having a VH and a VL of a CD8 antibody provided herein. In one embodiment, provided is an antibody having a heavy chain of a CD8 antibody provided herein. In one embodiment, provided is an antibody having a light chain of a CD8 antibody provided herein. In one embodiment, provided is an antibody having a heavy chain and a light chain of a CD8 antibody provided herein.


In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:31. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:32. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:31; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:32. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:65. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:66. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:65; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:66. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:99. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:100. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:99; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:100. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:133. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:134. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:133; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:134. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:167. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:168. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:167; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:168. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:201. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:202. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:201; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:202. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:235. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:236. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:235; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:236. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:269. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:270. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:269; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:270. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:303. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:304. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:303; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:304. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:337. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:338. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:337; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:338. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:371. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:372. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:371; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:372. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:405. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:406. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:405; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:406. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:439. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:440. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:439; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:440. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:473. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:474. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:473; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:474. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:507. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:508. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:507; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:508. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:541. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:542. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:541; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:542. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:575. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:576. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:575; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:576. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:609. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:610. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:609; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:610. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:643. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:644. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:643; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:644. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:677. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:678. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:677; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:678. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:711. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:712. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:711; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:712. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:745. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:746. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:745; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:746. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:779. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:780. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:779; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:780. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:813. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:814. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:813; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:814. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:847. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:848. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:847; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:848. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:881. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:882. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:881; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:882. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:915. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:916. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:915; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:916. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:949. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:950. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:949; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:950. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:983. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:984. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:983; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:984. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1017. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1018. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1017; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1018. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1051. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1052. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1051; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1052. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1085. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1086. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1085; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1086. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1119. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1120. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1119; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1120. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1153. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1154. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1153; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1154. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1187. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1188. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1187; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1188. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1221. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1222. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1221; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1222. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1255. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1256. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1255; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1256. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1289. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1290. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1289; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1290. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1323. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1324. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1323; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1324. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1357. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1358. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1357; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1358. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1391. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1392. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1391; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1392. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1425. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1426. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1425; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1426. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1459. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1460. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1459; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1460. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1493. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1494. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1493; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1494. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1527. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1528. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1527; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1528. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1561. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1562. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1561; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1562. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1595. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1596. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1595; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1596. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1629. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1630. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1629; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1630. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1663. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1664. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1663; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1664. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1697. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1698. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1697; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1698. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1731. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1732. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1731; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1732. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1765. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1766. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1765; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1766. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1799. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1800. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1799; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1800. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1833. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1834. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1833; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1834. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1867. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1868. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1867; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1868. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1901. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1902. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1901; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1902. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1935. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1936. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1935; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1936. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1969. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1970. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1969; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1970. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2003. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2004. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2003; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2004. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2037. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2038. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2037; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2038. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2071. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2072. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2071; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2072. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2105. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2106. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2105; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2106. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2139. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2140. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2139; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2140. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2173. In one embodiment, the CD8 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2174. In one embodiment, the CD8 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2173; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2174. In some embodiments, the CD8 antibody is a multispecific antibody. In some embodiments, the CD8 antibody is a bispecific antibody. In some embodiments, the CD8 antibody is a trispecific antibody. In some embodiments, the CD8 antibody is a quadraspecific antibody. In certain embodiments, the CD8 antibody is a multispecific antibody, wherein the second target is CD4. In certain embodiments, the CD8×CD4 multispecific antibody comprises a CD8 antibody provided herein and a CD4 antibody provided here.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1, 2, and 3, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4, 5, and 6, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:7, 8, and 9, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:10, 11, and 12, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:13, 14, and 15, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:16, 17, and 18, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:19, 20, and 21, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:22, 23, and 24, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:25, 26, and 27, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:28, 29, and 30, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:31; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:32. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:31. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:32. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:31, and a VL having an amino acid sequence of SEQ ID NO:32. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:33. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:34. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:33, and a light chain having an amino acid sequence of SEQ ID NO:34. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:31. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:32. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:31, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:32. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:33. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:34. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:33, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:34.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:35, 36, and 37, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:38, 39, and 40, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:41, 42, and 43, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:44, 45, and 46, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:47, 48, and 49, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:50, 51, and 52, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:53, 54, and 55, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:56, 57, and 58, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:59, 60, and 61, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:62, 63, and 64, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:65; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:66. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:65. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:66. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:65, and a VL having an amino acid sequence of SEQ ID NO:66. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:67. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:68. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:67, and a light chain having an amino acid sequence of SEQ ID NO:68. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:65. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:66. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:65, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:66. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:67. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:68. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:67, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:68.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:69, 70, and 71, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:72, 73, and 74, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:75, 76, and 77, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:78, 79, and 80, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:81, 82, and 83, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:84, 85, and 86, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:87, 88, and 89, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:90, 91, and 92, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:93, 94, and 95, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:96, 97, and 98, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:99; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:100. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:99. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:100. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:99, and a VL having an amino acid sequence of SEQ ID NO:100. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:101. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:102. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:101, and a light chain having an amino acid sequence of SEQ ID NO:102. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:99. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:100. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:99, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:100. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:101. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:102. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:101, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:102.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:103, 104, and 105, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:106, 107, and 108, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:109, 110, and 111, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:112, 113, and 114, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:115, 116, and 117, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:118, 119, and 120, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:121, 122, and 123, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:124, 125, and 126, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:127, 128, and 129, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:130, 131, and 132, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:133; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:134. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:133. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:134. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:133, and a VL having an amino acid sequence of SEQ ID NO:134. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:135. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:136. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:135, and a light chain having an amino acid sequence of SEQ ID NO:136. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:133. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:134. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:133, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:134. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:135. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:136. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:135, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:136.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:137, 138, and 139, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:140, 141, and 142, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:143, 144, and 145, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:146, 147, and 148, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:149, 150, and 151, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:152, 153, and 154, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:155, 156, and 157, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:158, 159, and 160, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:161, 162, and 163, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:164, 165, and 166, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:167; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:168. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:167. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:168. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:167, and a VL having an amino acid sequence of SEQ ID NO:168. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:169. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:170. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:169, and a light chain having an amino acid sequence of SEQ ID NO:170. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:167. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:168. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:167, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:168. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:169. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:170. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:169, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:170.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:171, 172, and 173, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:174, 175, and 176, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:177, 178, and 179, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:180, 181, and 182, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:183, 184, and 185, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:186, 187, and 188, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:189, 190, and 191, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:192, 193, and 194, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:195, 196, and 197, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:198, 199, and 200, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:201; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:202. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:201. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:202. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:201, and a VL having an amino acid sequence of SEQ ID NO:202. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:203. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:204. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:203, and a light chain having an amino acid sequence of SEQ ID NO:204. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:201. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:202. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:201, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:202. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:203. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:204. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:203, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:204.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:205, 206, and 207, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:208, 209, and 210, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:211, 212, and 213, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:214, 215, and 216, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:217, 218, and 219, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:220, 221, and 222, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:223, 224, and 225, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:226, 227, and 228, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:229, 230, and 231, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:232, 233, and 234, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:235; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:236. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:235. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:236. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:235, and a VL having an amino acid sequence of SEQ ID NO:236. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:237. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:238. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:237, and a light chain having an amino acid sequence of SEQ ID NO:238. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:235. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:236. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:235, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:236. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:237. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:238. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:237, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:238.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:239, 240, and 241, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:242, 243, and 244, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:245, 246, and 247, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:248, 249, and 250, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:251, 252, and 253, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:254, 255, and 256, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:257, 258, and 259, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:260, 261, and 262, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:263, 264, and 265, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:266, 267, and 268, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:269; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:270. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:269. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:270. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:269, and a VL having an amino acid sequence of SEQ ID NO:270. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:271. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:272. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:271, and a light chain having an amino acid sequence of SEQ ID NO:272. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:269. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:270. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:269, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:270. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:271. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:272. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:271, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:272.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:273, 274, and 275, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:276, 277, and 278, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:279, 280, and 281, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:282, 283, and 284, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:285, 286, and 287, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:288, 289, and 290, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:291, 292, and 293, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:294, 295, and 296, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:297, 298, and 299, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:300, 301, and 302, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:303; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:304. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:303. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:304. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:303, and a VL having an amino acid sequence of SEQ ID NO:304. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:305. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:306. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:305, and a light chain having an amino acid sequence of SEQ ID NO:306. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:303. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:304. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:303, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:304. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:305. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:306. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:305, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:306.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:307, 308, and 309, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:310, 311, and 312, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:313, 314, and 315, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:316, 317, and 318, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:319, 320, and 321, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:322, 323, and 324, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:325, 326, and 327, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:328, 329, and 330, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:331, 332, and 333, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:334, 335, and 336, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:337; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:338. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:337. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:338. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:337, and a VL having an amino acid sequence of SEQ ID NO:338. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:339. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:340. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:339, and a light chain having an amino acid sequence of SEQ ID NO:340. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:337. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:338. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:337, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:338. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:339. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:340. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:339, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:340.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:341, 342, and 343, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:344, 345, and 346, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:347, 348, and 349, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:350, 351, and 352, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:353, 354, and 355, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:356, 357, and 358, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:359, 360, and 361, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:362, 363, and 364, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:365, 366, and 367, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:368, 369, and 370, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:371; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:372. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:371. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:372. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:371, and a VL having an amino acid sequence of SEQ ID NO:372. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:373. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:374. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:373, and a light chain having an amino acid sequence of SEQ ID NO:374. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:371. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:372. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:371, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:372. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:373. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:374. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:373, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:374.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:375, 376, and 377, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:378, 379, and 380, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:381, 382, and 383, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:384, 385, and 386, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:387, 388, and 389, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:390, 391, and 392, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:393, 394, and 395, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:396, 397, and 398, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:399, 400, and 401, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:402, 403, and 404, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:405; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:406. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:405. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:406. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:405, and a VL having an amino acid sequence of SEQ ID NO:406. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:407. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:408. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:407, and a light chain having an amino acid sequence of SEQ ID NO:408. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:405. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:406. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:405, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:406. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:407. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:408. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:407, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:408.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:409, 410, and 411, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:412, 413, and 414, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:415, 416, and 417, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:418, 419, and 420, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:421, 422, and 423, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:424, 425, and 426, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:427, 428, and 429, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:430, 431, and 432, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:433, 434, and 435, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:436, 437, and 438, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:439; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:440. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:439. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:440. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:439, and a VL having an amino acid sequence of SEQ ID NO:440. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:441. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:442. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:441, and a light chain having an amino acid sequence of SEQ ID NO:442. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:439. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:440. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:439, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:440. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:441. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:442. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:441, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:442.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:443, 444, and 445, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:446, 447, and 448, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:449, 450, and 451, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:452, 453, and 454, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:455, 456, and 457, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:458, 459, and 460, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:461, 462, and 463, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:464, 465, and 466, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:467, 468, and 469, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:470, 471, and 472, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:473; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:474. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:473. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:474. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:473, and a VL having an amino acid sequence of SEQ ID NO:474. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:475. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:476. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:475, and a light chain having an amino acid sequence of SEQ ID NO:476. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:473. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:474. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:473, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:474. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:475. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:476. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:475, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:476.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:477, 478, and 479, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:480, 481, and 482, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:483, 484, and 485, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:486, 487, and 488, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:489, 490, and 491, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:492, 493, and 494, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:495, 496, and 497, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:498, 499, and 500, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:501, 502, and 503, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:504, 505, and 506, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:507; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:508. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:507. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:508. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:507, and a VL having an amino acid sequence of SEQ ID NO:508. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:509. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:510. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:509, and a light chain having an amino acid sequence of SEQ ID NO:510. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:507. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:508. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:507, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:508. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:509. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:510. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:509, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:510.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:511, 512, and 513, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:514, 515, and 516, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:517, 518, and 519, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:520, 521, and 522, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:523, 524, and 525, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:526, 527, and 528, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:529, 530, and 531, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:532, 533, and 534, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:535, 536, and 537, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:538, 539, and 540, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:541; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:542. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:541. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:542. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:541, and a VL having an amino acid sequence of SEQ ID NO:542. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:543. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:544. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:543, and a light chain having an amino acid sequence of SEQ ID NO:544. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:541. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:542. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:541, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:542. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:543. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:544. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:543, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:544.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:545, 546, and 547, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:548, 549, and 550, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:551, 552, and 553, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:554, 555, and 556, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:557, 558, and 559, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:560, 561, and 562, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:563, 564, and 565, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:566, 567, and 568, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:569, 570, and 571, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:572, 573, and 574, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:575; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:576. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:575. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:576. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:575, and a VL having an amino acid sequence of SEQ ID NO:576. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:577. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:578. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:577, and a light chain having an amino acid sequence of SEQ ID NO:578. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:575. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:576. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:575, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:576. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:577. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:578. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:577, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:578.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:579, 580, and 581, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:582, 583, and 584, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:585, 586, and 587, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:588, 589, and 590, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:591, 592, and 593, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:594, 595, and 596, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:597, 598, and 599, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:600, 601, and 602, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:603, 604, and 605, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:606, 607, and 608, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:609; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:610. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:609. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:610. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:609, and a VL having an amino acid sequence of SEQ ID NO:610. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:611. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:612. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:611, and a light chain having an amino acid sequence of SEQ ID NO:612. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:609. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:610. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:609, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:610. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:611. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:612. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:611, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:612.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:613, 614, and 615, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:616, 617, and 618, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:619, 620, and 621, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:622, 523, and 624, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:625, 626, and 627, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:628, 629, and 630, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:631, 632, and 633, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:634, 635, and 636, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:637, 638, and 639, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:640, 641, and 642, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:643; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:644. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:643. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:644. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:643, and a VL having an amino acid sequence of SEQ ID NO:644. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:645. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:646. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:645, and a light chain having an amino acid sequence of SEQ ID NO:646. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:643. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:644. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:643, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:644. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:645. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:646. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:645, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:646.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:647, 648, and 649, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:650, 651, and 652, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:653, 654, and 655, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:656, 657, and 658, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:659, 660, and 661, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:662, 663, and 664, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:665, 666, and 667, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:668, 669, and 670, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:671, 672, and 673, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:674, 675, and 676, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:677; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:678. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:677. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:678. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:677, and a VL having an amino acid sequence of SEQ ID NO:678. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:679. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:680. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:679, and a light chain having an amino acid sequence of SEQ ID NO:680. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:677. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:678. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:677, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:678. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:679. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:680. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:679, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:680.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:681, 682, and 683, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:684, 685, and 686, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:687, 688, and 689, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:690, 691, and 692, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:693, 694, and 695, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:696, 697, and 698, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:699, 700, and 701, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:702, 703, and 704, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:705, 706, and 707, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:708, 709, and 710, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:711; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:712. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:711. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:712. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:711, and a VL having an amino acid sequence of SEQ ID NO:712. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:713. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:714. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:713, and a light chain having an amino acid sequence of SEQ ID NO:714. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:711. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:712. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:711, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:712. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:713. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:714. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:713, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:714.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:715, 716, and 717, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:718, 719, and 720, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:721, 722, and 723, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:724, 725, and 726, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:727, 728, and 729, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:730, 731, and 732, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:733, 734, and 735, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:736, 737, and 738, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:739, 740, and 741, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:742, 743, and 744, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:745; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:746. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:745. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:746. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:745, and a VL having an amino acid sequence of SEQ ID NO:746. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:747. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:748. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:747, and a light chain having an amino acid sequence of SEQ ID NO:748. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:745. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:746. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:745, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:746. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:747. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:748. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:747, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:748.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:749, 750, and 751, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:752, 753, and 754, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:755, 756, and 757, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:758, 759, and 760, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:761, 762, and 763, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:764, 765, and 766, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:767, 768, and 769, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:770, 771, and 772, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:773, 774, and 775, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:776, 777, and 778, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:779; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:780. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:779. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:780. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:779, and a VL having an amino acid sequence of SEQ ID NO:780. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:781. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:782. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:781, and a light chain having an amino acid sequence of SEQ ID NO:782. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:779. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:780. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:779, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:780. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:781. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:782. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:781, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:782.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:783, 784, and 785, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:786, 787, and 788, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:789, 790, and 791, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:792, 793, and 794, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:795, 796, and 797, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:798, 799, and 800, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:801, 802, and 803, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:804, 805, and 806, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:807, 808, and 809, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:810, 811, and 812, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:813; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:814. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:813. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:814. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:813, and a VL having an amino acid sequence of SEQ ID NO:814. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:815. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:816. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:815, and a light chain having an amino acid sequence of SEQ ID NO:816. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:813. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:814. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:813, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:814. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:815. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:816. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:815, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:816.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:817, 818, and 819, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:820, 821, and 822, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:823, 824, and 825, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:826, 827, and 828, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:829, 830, and 831, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:832, 833, and 834, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:835, 836, and 837, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:838, 839, and 840, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:841, 842, and 843, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:844, 845, and 846, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:847; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:848. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:847. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:848. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:847, and a VL having an amino acid sequence of SEQ ID NO:848. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:849. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:850. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:849, and a light chain having an amino acid sequence of SEQ ID NO:850. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:847. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:848. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:847, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:848. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:849. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:850. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:849, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:850.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:851, 852, and 853, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:854, 855, and 856, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:857, 858, and 859, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:860, 861, and 862, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:863, 864, and 865, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:866, 867, and 868, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:869, 870, and 871, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:872, 873, and 874, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:875, 876, and 877, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:878, 879, and 880, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:881; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:882. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:881. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:882. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:881, and a VL having an amino acid sequence of SEQ ID NO:882. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:883. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:884. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:883, and a light chain having an amino acid sequence of SEQ ID NO:884. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:881. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:882. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:881, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:882. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:883. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:884. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:883, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:884.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:885, 886, and 887, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:888, 889, and 890, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:891, 892, and 893, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:894, 895, and 896, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:897, 898, and 899, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:900, 901, and 902, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:903, 904, and 905, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:906, 907, and 908, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:909, 910, and 911, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:912, 913, and 914, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:915; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:916. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:915. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:916. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:915, and a VL having an amino acid sequence of SEQ ID NO:916. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:917. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:918. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:917, and a light chain having an amino acid sequence of SEQ ID NO:918. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:915. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:916. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:915, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:916. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:917. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:918. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:917, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:918.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:919, 920, and 921, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:922, 923, and 924, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:925, 926, and 927, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:928, 929, and 930, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:931, 932, and 933, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:934, 935, and 936, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:937, 938, and 939, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:940, 941, and 942, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:943, 944, and 945, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:946, 947, and 948, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:949; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:950. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:949. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:950. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:949, and a VL having an amino acid sequence of SEQ ID NO:950. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:951. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:952. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:951, and a light chain having an amino acid sequence of SEQ ID NO:952. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:949. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:950. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:949, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:950. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:951. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:952. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:951, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:952.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:953, 954, and 955, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:956, 957, and 958, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:959, 960, and 961, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:962, 963, and 964, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:965, 966, and 967, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:968, 969, and 970, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:971, 972, and 973, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:974, 975, and 976, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:977, 978, and 979, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:980, 981, and 982, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:983; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:984. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:983. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:984. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:983, and a VL having an amino acid sequence of SEQ ID NO:984. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:985. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:986. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:985, and a light chain having an amino acid sequence of SEQ ID NO:986. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:983. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:984. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:983, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:984. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:985. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:986. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:985, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:986.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:987, 988, and 989, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:990, 991, and 992, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:993, 994, and 995, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:996, 997, and 998, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:999, 1000, and 1001, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1002, 1003, and 1004, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1005, 1006, and 1007, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1008, 1009, and 1010, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1011, 1012, and 1013, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1014, 1015, and 1016, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1017; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1018. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1017. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:1018. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1017, and a VL having an amino acid sequence of SEQ ID NO:1018. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1019. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:1020. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1019, and a light chain having an amino acid sequence of SEQ ID NO:1020. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1017. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1018. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1017, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1018. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1019. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1020. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1019, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1020.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1021, 1022, and 1023, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1024, 1025, and 1026, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1027, 1028, and 1029, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1030, 1031, and 1032, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1033, 1034, and 1035, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1036, 1037, and 1038, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1039, 1040, and 1041, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1042, 1043, and 1044, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1045, 1046, and 1047, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1048, 1049, and 1050, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1051; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1052. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1051. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:1052. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1051, and a VL having an amino acid sequence of SEQ ID NO:1052. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1053. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:1054. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1053, and a light chain having an amino acid sequence of SEQ ID NO:1054. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1051. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1052. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1051, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1052. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1053. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1054. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1053, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1054.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1055, 1056, and 1057, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1058, 1059, and 1060, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1061, 1062, and 1063, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1064, 1065, and 1066, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1067, 1068, and 1069, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1070, 1071, and 1072, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1073, 1074, and 1075, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1076, 1077, and 1078, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1079, 1080, and 1081, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1082, 1083, and 1084, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1085; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1086. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1085. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:1086. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1085, and a VL having an amino acid sequence of SEQ ID NO:1086. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1087. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:1088. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1087, and a light chain having an amino acid sequence of SEQ ID NO:1088. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1085. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1086. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1085, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1086. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1087. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1088. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1087, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1088.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1089, 1090, and 1091, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1092, 1093, and 1094, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1095, 1096, and 1097, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1098, 1099, and 1100, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1101, 1102, and 1103, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1104, 1105, and 1106, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1107, 1108, and 1109, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1110, 1111, and 1112, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1113, 1114, and 1115, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1116, 1117, and 1118, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1119; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1120. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1119. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:1120. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1119, and a VL having an amino acid sequence of SEQ ID NO:1120. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1121. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:1122. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1121, and a light chain having an amino acid sequence of SEQ ID NO:1122. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1119. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1120. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1119, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1120. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1121. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1122. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1121, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1122.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1123, 1124, and 1125, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1126, 1127, and 1128, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1129, 1130, and 1131, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1132, 1133, and 1134, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1135, 1136, and 1137, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1138, 1139, and 1140, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1141, 1142, and 1143, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1144, 1145, and 1146, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1147, 1148, and 1149, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1150, 1151, and 1152, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1153; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1154. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1153. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:1154. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1153, and a VL having an amino acid sequence of SEQ ID NO:1154. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1155. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:1156. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1155, and a light chain having an amino acid sequence of SEQ ID NO:1156. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1153. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1154. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1153, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1154. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1155. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1156. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1155, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1156.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1157, 1158, and 1159, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1160, 1161, and 1162, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1163, 1164, and 1165, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1166, 1167, and 1168, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1169, 1170, and 1171, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1172, 1173, and 1174, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1175, 1176, and 1177, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1178, 1179, and 1180, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1181, 1182, and 1183, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1184, 1185, and 1186, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1187; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1188. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1187. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:1188. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1187, and a VL having an amino acid sequence of SEQ ID NO:1188. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1189. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:1190. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1189, and a light chain having an amino acid sequence of SEQ ID NO:1190. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1187. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO: 1188. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1187, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1188. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1189. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1190. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1189, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1190.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1191, 1192, and 1193, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1194, 1195, and 1196, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1197, 1198, and 1199, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1200, 1201, and 1202, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1203, 1204, and 1205, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1206, 1207, and 1208, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1209, 1210, and 1211, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1212, 1213, and 1214, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1215, 1216, and 1217, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1218, 1219, and 1220, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1221; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1222. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1221. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:1222. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1221, and a VL having an amino acid sequence of SEQ ID NO:1222. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1223. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:1224. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1223, and a light chain having an amino acid sequence of SEQ ID NO:1224. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1221. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1222. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1221, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1222. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1223. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1224. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1223, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1224.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1225, 1226, and 1227, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1228, 1229, and 1230, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1231, 1232, and 1233, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1234, 1235, and 1236, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1237, 1238, and 1239, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1240, 1241, and 1242, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1243, 1244, and 1245, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1246, 1247, and 1248, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1249, 1250, and 1251, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1252, 1253, and 1254, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1255; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1256. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1255. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:1256. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1255, and a VL having an amino acid sequence of SEQ ID NO:1256. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1257. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:1258. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1257, and a light chain having an amino acid sequence of SEQ ID NO:1258. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1255. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1256. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1255, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1256. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1257. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1258. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1257, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1258.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1259, 1260, and 1261, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1262, 1263, and 1264, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1265, 1266, and 1267, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1268, 1269, and 1270, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1271, 1272, and 1273, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1274, 1275, and 1276, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1277, 1278, and 1279, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1280, 1281, and 1282, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1283, 1284, and 1285, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1286, 1287, and 1288, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1289; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1290. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1289. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:1290. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1289, and a VL having an amino acid sequence of SEQ ID NO:1290. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1291. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:1292. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1291, and a light chain having an amino acid sequence of SEQ ID NO:1292. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1289. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1290. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1289, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1290. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1291. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1292. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1291, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1292.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1293, 1294, and 1295, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1296, 1297, and 1298, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1299, 1300, and 1301, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1302, 1303, and 1304, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1305, 1306, and 1307, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1308, 1309, and 1310, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1311, 1312, and 1313, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1314, 1315, and 1316, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1317, 1318, and 1319, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1320, 1321, and 1322, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1323; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1324. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1323. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:1324. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1323, and a VL having an amino acid sequence of SEQ ID NO:1324. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1325. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:1326. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1325, and a light chain having an amino acid sequence of SEQ ID NO:1326. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1323. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1324. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1323, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1324. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1325. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1326. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1325, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1326.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1327, 1328, and 1329, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1330, 1331, and 1332, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1333, 1334, and 1335, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1336, 1337, and 1338, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1339, 1340, and 1341, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1342, 1343, and 1344, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1345, 1346, and 1347, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1348, 1349, and 1350, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1351, 1352, and 1353, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1354, 1355, and 1356, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1357; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1358. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1357. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:1358. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1357, and a VL having an amino acid sequence of SEQ ID NO:1358. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1359. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:1360. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1359, and a light chain having an amino acid sequence of SEQ ID NO:1360. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1357. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1358. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1357, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1358. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1359. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1360. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1359, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1360.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1361, 1362, and 1363, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1364, 1365, and 1366, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1367, 1368, and 1369, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1370, 1371, and 1372, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1373, 1374, and 1375, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1376, 1377, and 1378, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1379, 1380, and 1381, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1382, 1383, and 1384, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1385, 1386, and 1387, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1388, 1389, and 1390, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1391; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1392. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1391. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:1392. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1391, and a VL having an amino acid sequence of SEQ ID NO:1392. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1393. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:1394. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1393, and a light chain having an amino acid sequence of SEQ ID NO:1394. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1391. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1392. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1391, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1392. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1393. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1394. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1393, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1394.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1395, 1396, and 1397, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1398, 1399, and 1400, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1401, 1402, and 1403, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1404, 1405, and 1406, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1407, 1408, and 1409, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1410, 1411, and 1412, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1413, 1414, and 1415, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1416, 1417, and 1418, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1419, 1420, and 1421, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1422, 1423, and 1424, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1425; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1426. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1425. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:1426. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1425, and a VL having an amino acid sequence of SEQ ID NO:1426. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1427. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:1428. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1427, and a light chain having an amino acid sequence of SEQ ID NO:1428. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1425. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1426. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1425, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1426. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1427. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1428. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1427, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1428.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1429, 1430, and 1431, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1432, 1433, and 1434, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1435, 1436, and 1437, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1438, 1439, and 1440, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1441, 1442, and 1443, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1444, 1445, and 1446, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1447, 1448, and 1449, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1450, 1451, and 1452, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1453, 1454, and 1455, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1456, 1457, and 1458, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1459; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1460. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1459. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:1460. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1459, and a VL having an amino acid sequence of SEQ ID NO:1460. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1461. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:1462. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1461, and a light chain having an amino acid sequence of SEQ ID NO:1462. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1459. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1460. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1459, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1460. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1461. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1462. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1461, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1462.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1463, 1464, and 1465, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1466, 1467, and 1468, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1469, 1470, and 1471, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1472, 1473, and 1474, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1475, 1476, and 1477, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1478, 1479, and 1480, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1481, 1482, and 1483, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1484, 1485, and 1486, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1487, 1488, and 1489, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1490, 1491, and 1492, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1493; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1494. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1493. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:1494. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1493, and a VL having an amino acid sequence of SEQ ID NO:1494. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1495. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:1496. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1495, and a light chain having an amino acid sequence of SEQ ID NO:1496. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1493. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1494. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1493, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1494. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1495. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1496. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1495, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1496.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1497, 1498, and 1499, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1500, 1501, and 1502, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1503, 1504, and 1505, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1506, 1507, and 1508, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1509, 1510, and 1511, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1512, 1513, and 1514, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1515, 1516, and 1517, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1518, 1519, and 1520, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1521, 1522, and 1523, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1524, 1525, and 1526, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1527; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1528. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1527. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:1528. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1527, and a VL having an amino acid sequence of SEQ ID NO:1528. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1529. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:1530. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1529, and a light chain having an amino acid sequence of SEQ ID NO:1530. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1527. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1528. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1527, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1528. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1529. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1530. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1529, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1530.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1531, 1532, and 1533, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1534, 1535, and 1536, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1537, 1538, and 1539, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1540, 1541, and 1542, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1543, 1544, and 1545, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1546, 1547, and 1548, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1549, 1550, and 1551, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1552, 1553, and 1554, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1555, 1556, and 1557, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1558, 1559, and 1560, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1561; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1562. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1561. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:1562. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1561, and a VL having an amino acid sequence of SEQ ID NO:1562. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1563. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:1564. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1563, and a light chain having an amino acid sequence of SEQ ID NO:1564. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1561. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1562. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1561, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1562. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1563. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1564. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1563, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1564.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1565, 1566, and 1567, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1568, 1569, and 1570, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1571, 1572, and 1573, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1574, 1575, and 1576, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1577, 1578, and 1579, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1580, 1581, and 1582, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1583, 1584, and 1585, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1586, 1587, and 1588, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1589, 1590, and 1591, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1592, 1593, and 1594, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1595; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1596. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1595. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:1596. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1595, and a VL having an amino acid sequence of SEQ ID NO:1596. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1597. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:1598. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1597, and a light chain having an amino acid sequence of SEQ ID NO:1598. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1595. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1596. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1595, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1596. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1597. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1598. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1597, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1598.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1599, 1600, and 1601, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1602, 1603, and 1604, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1605, 1606, and 1607, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1608, 1609, and 1610, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1611, 1612, and 1613, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1614, 1615, and 1616, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1617, 1618, and 1619, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1620, 1621, and 1622, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1623, 1624, and 1625, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1626, 1627, and 1628, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1629; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1630. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1629. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:1630. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1629, and a VL having an amino acid sequence of SEQ ID NO:1630. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1631. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:1632. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1631, and a light chain having an amino acid sequence of SEQ ID NO:1632. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1629. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1630. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1629, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1630. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1631. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1632. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1631, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1632.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1633, 1634, and 1635, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1636, 1637, and 1638, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1639, 1640, and 1641, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1642, 1643, and 1644, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1645, 1646, and 1647, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1648, 1649, and 1650, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1651, 1652, and 1653, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1654, 1655, and 1656, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1657, 1658, and 1659, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1660, 1661, and 1662, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1663; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1664. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1663. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:1664. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1663, and a VL having an amino acid sequence of SEQ ID NO:1664. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1665. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:1666. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1665, and a light chain having an amino acid sequence of SEQ ID NO:1666. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1663. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1664. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1663, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1664. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1665. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1666. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1665, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1666.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1667, 1668, and 1669, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1670, 1671, and 1672, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1673, 1674, and 1675, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1676, 1677, and 1678, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1679, 1680, and 1681, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1682, 1683, and 1684, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1685, 1686, and 1687, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1688, 1689, and 1690, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1691, 1692, and 1693, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1694, 1695, and 1696, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1697; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1698. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1697. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:1698. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1697, and a VL having an amino acid sequence of SEQ ID NO:1698. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1699. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:1700. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1699, and a light chain having an amino acid sequence of SEQ ID NO:1700. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1697. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1698. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1697, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1698. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1699. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1700. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1699, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1700.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1701, 1702, and 1703, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1704, 1705, and 1706, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1707, 1708, and 1709, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1710, 1711, and 1712, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1713, 1714, and 1715, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1716, 1717, and 1718, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1719, 1720, and 1721, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1722, 1723, and 1724, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1725, 1726, and 1727, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1728, 1729, and 1730, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1731; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1732. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1731. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:1732. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1731, and a VL having an amino acid sequence of SEQ ID NO:1732. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1733. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:1734. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1733, and a light chain having an amino acid sequence of SEQ ID NO:1734. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1731. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1732. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1731, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1732. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1733. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1734. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1733, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1734.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1735, 1736, and 1737, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1738, 1739, and 1740, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1741, 1742, and 1743, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1744, 1745, and 1746, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1747, 1748, and 1749, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1750, 1751, and 1752, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1753, 1754, and 1755, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1756, 1757, and 1758, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1759, 1760, and 1761, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1762, 1763, and 1764, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1765; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1766. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1765. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:1766. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1765, and a VL having an amino acid sequence of SEQ ID NO:1766. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1767. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:1768. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1767, and a light chain having an amino acid sequence of SEQ ID NO:1768. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1765. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1766. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1765, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1766. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1767. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1768. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1767, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1768.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1769, 1770, and 1771, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1772, 1773, and 1774, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1775, 1776, and 1777, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1778, 1779, and 1780, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1781, 1782, and 1783, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1784, 1785, and 1786, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1787, 1788, and 1789, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1790, 1791, and 1792, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1793, 1794, and 1795, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1796, 1797, and 1798, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1799; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1800. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1799. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:1800. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1799, and a VL having an amino acid sequence of SEQ ID NO:1800. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1801. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:1802. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1801, and a light chain having an amino acid sequence of SEQ ID NO:1802. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1799. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1800. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1799, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1800. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1801. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1802. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1801, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1802.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1803, 1804, and 1805, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1806, 1807, and 1808, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1809, 1810, and 1811, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1812, 1813, and 1814, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1815, 1816, and 1817, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1818, 1819, and 1820, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1821, 1822, and 1823, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1824, 1825, and 1826, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1827, 1828, and 1829, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1830, 1831, and 1832, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1833; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1834. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1833. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:1834. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1833, and a VL having an amino acid sequence of SEQ ID NO:1834. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1835. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:1836. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1835, and a light chain having an amino acid sequence of SEQ ID NO:1836. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1833. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1834. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1833, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1834. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1835. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1836. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1835, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1836.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1837, 1838, and 1839, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1840, 1841, and 1842, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1843, 1844, and 1845, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1846, 1847, and 1848, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1849, 1850, and 1851, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1852, 1853, and 1854, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1855, 1856, and 1857, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1858, 1859, and 1860, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1861, 1862, and 1863, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1864, 1865, and 1866, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1867; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1868. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1867. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:1868. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1867, and a VL having an amino acid sequence of SEQ ID NO:1868. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1869. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:1870. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1869, and a light chain having an amino acid sequence of SEQ ID NO:1870. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1867. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1868. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1867, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1868. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1869. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1870. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1869, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1870.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1871, 1872, and 1873, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1874, 1875, and 1876, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1877, 1878, and 1879, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1880, 1881, and 1882, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1883, 1884, and 1885, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1886, 1887, and 1888, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1889, 1890, and 1891, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1892, 1893, and 1894, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1895, 1896, and 1897, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1898, 1899, and 1900, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1901; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1902. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1901. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:1902. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1901, and a VL having an amino acid sequence of SEQ ID NO:1902. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1903. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:1904. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1903, and a light chain having an amino acid sequence of SEQ ID NO:1904. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1901. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1902. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1901, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1902. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1903. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1904. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1903, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1904.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1905, 1906, and 1907, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1908, 1909, and 1910, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1911, 1912, and 1913, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1914, 1915, and 1916, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1917, 1918, and 1919, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1920, 1921, and 1922, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1923, 1924, and 1925, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1926, 1927, and 1928, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1929, 1930, and 1931, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1932, 1933, and 1934, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1935; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1936. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1935. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:1936. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1935, and a VL having an amino acid sequence of SEQ ID NO:1936. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1937. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:1938. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1937, and a light chain having an amino acid sequence of SEQ ID NO:1938. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1935. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1936. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1935, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1936. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1937. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1938. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1937, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1938.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1939, 1940, and 1941, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1942, 1943, and 1944, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1945, 1946, and 1947, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1948, 1949, and 1950, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1951, 1952, and 1953, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1954, 1955, and 1956, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1957, 1958, and 1959, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1960, 1961, and 1962, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1963, 1964, and 1965, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1966, 1967, and 1968, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1969; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1970. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1969. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:1970. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:1969, and a VL having an amino acid sequence of SEQ ID NO:1970. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1971. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:1972. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:1971, and a light chain having an amino acid sequence of SEQ ID NO:1972. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1969. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1970. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1969, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1970. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1971. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1972. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1971, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:1972.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1973, 1974, and 1975, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1976, 1977, and 1978, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1979, 1980, and 1981, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1982, 1983, and 1984, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1985, 1986, and 1987, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1988, 1989, and 1990, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1991, 1992, and 1993, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:1994, 1995, and 1996, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:1997, 1998, and 1999, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2000, 2001, and 2002, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2003; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2004. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:2003. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:2004. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:2003, and a VL having an amino acid sequence of SEQ ID NO:2004. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:2005. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:2006. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:2005, and a light chain having an amino acid sequence of SEQ ID NO:2006. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2003. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2004. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2003, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2004. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2005. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2006. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2005, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2006.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2007, 2008, and 2009, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2010, 2011, and 2012, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2013, 2014, and 2015, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2016, 2017, and 2018, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2019, 2020, and 2021, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2022, 2023, and 2024, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2025, 2026, and 2027, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2028, 2029, and 2030, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2031, 2032, and 2033, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2034, 2035, and 2036, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2037; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2038. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:2037. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:2038. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:2037, and a VL having an amino acid sequence of SEQ ID NO:2038. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:2039. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:2040. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:2039, and a light chain having an amino acid sequence of SEQ ID NO:2040. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2037. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2038. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2037, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2038. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2039. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2040. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2039, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2040.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2041, 2042, and 2043, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2044, 2045, and 2046, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2047, 2048, and 2049, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2050, 2051, and 2052, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2053, 2054, and 2055, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2056, 2057, and 2058, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2059, 2060, and 2061, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2062, 2063, and 2064, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2065, 2066, and 2067, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2068, 2069, and 2070, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2071; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2072. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:2071. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:2072. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:2071, and a VL having an amino acid sequence of SEQ ID NO:2072. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:2073. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:2074. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:2073, and a light chain having an amino acid sequence of SEQ ID NO:2074. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2071. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2072. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2071, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2072. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2073. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2074. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2073, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2074.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2075, 2076, and 2077, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2078, 2079, and 2080, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2081, 2082, and 2083, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2084, 2085, and 2086, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2087, 2088, and 2089, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2090, 2091, and 2092, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2093, 2094, and 2095, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2096, 2097, and 2098, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2099, 2100, and 2101, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2102, 2103, and 2104, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2105; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2106. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:2105. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:2106. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:2105, and a VL having an amino acid sequence of SEQ ID NO:2106. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:2107. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:2108. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:2107, and a light chain having an amino acid sequence of SEQ ID NO:2108. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2105. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2106. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2105, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2106. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2107. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2108. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2107, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2108.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2109, 2110, and 2111, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2112, 2113, and 2114, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2115, 2116, and 2117, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2118, 2119, and 2120, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2121, 2122, and 2123, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2124, 2125, and 2126, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2127, 2128, and 2129, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2130, 2131, and 2132, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2133, 2134, and 2135, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2136, 2137, and 2138, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2139; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2140. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:2139. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:2140. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:2139, and a VL having an amino acid sequence of SEQ ID NO:2140. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:2141. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:2142. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:2141, and a light chain having an amino acid sequence of SEQ ID NO:2142. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2139. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2140. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2139, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2140. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2141. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2142. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2141, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2142.


In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2143, 2144, and 2145, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2146, 2147, and 2148, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2149, 2150, and 2151, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2152, 2153, and 2154, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2155, 2156, and 2157, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2158, 2159, and 2160, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2161, 2162, and 2163, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2164, 2165, and 2166, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2167, 2168, and 2169, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2170, 2171, and 2172, respectively. In one aspect, provided herein is an antibody that binds CD8, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2173; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2174. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:2173. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence of SEQ ID NO:2174. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence of SEQ ID NO:2173, and a VL having an amino acid sequence of SEQ ID NO:2174. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:2175. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence of SEQ ID NO:2176. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence of SEQ ID NO:2175, and a light chain having an amino acid sequence of SEQ ID NO:2176. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2173. In one aspect, provided herein is an antibody that binds CD8, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2174. In one aspect, provided herein is an antibody that binds CD8, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2173, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2174. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2175. In one aspect, provided herein is an antibody that binds CD8, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2176. In one aspect, provided herein is an antibody that binds CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2175, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2176.


In one aspect, provided herein is an antibody that binds CD8, comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:25, wherein the third amino acid is S or T; a VH CDR2 having an amino acid sequence of SEQ ID NO:26, wherein the first amino acid is I or V, the fourth amino acid is N, R or S, the seventh amino acid is A, G or N, and the eighth amino acid is T or V; and a VH CDR3 having an amino acid sequence of SEQ ID NO:27, wherein the first amino acid is A or T, the fifth amino acid is F or Y, and the sixth amino acid is N, G or S. In one aspect, provided herein is an antibody that binds CD8, comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:28, wherein the second amino acid is A or T, the fifth amino acid is D, H or N, and the sixth amino acid is F or Y; a VL CDR2 having an amino acid sequence of SEQ ID NO:29; and a VL CDR3 having an amino acid sequence of SEQ ID NO:30, wherein the second amino acid is N or S. In one aspect, provided herein is an antibody that binds CD8, comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:25, wherein the third amino acid is S or T; a VH CDR2 having an amino acid sequence of SEQ ID NO:26, wherein the first amino acid is I or V, the fourth amino acid is N, R or S, the seventh amino acid is A, G or N, and the eighth amino acid is T or V; a VH CDR3 having an amino acid sequence of SEQ ID NO:27, wherein the first amino acid is A or T, the fifth amino acid is F or Y, and the sixth amino acid is N, G or S; a VL CDR1 having an amino acid sequence of SEQ ID NO:28, wherein the second amino acid is A or T, the fifth amino acid is D, H or N, and the sixth amino acid is F or Y; a VL CDR2 having an amino acid sequence of SEQ ID NO:29; and a VL CDR3 having an amino acid sequence of SEQ ID NO:30, wherein the second amino acid is N or S.


In one aspect, provided herein is an antibody that binds CD8, comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:229; a VH CDR2 having an amino acid sequence of SEQ ID NO:230; and a VH CDR3 having an amino acid sequence of SEQ ID NO:231, wherein the ninth amino acid is H or Y. In one aspect, provided herein is an antibody that binds CD8, comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:232, wherein the fourth amino acid is N, R, or S, and the fifth amino acid is I or P; a VL CDR2 having an amino acid sequence of SEQ ID NO:233, wherein the first amino acid is F, H or Y; and a VL CDR3 having an amino acid sequence of SEQ ID NO:234. In one aspect, provided herein is an antibody that binds CD8, comprising: a VH CDR1 having an amino acid sequence of SEQ ID NO:229; a VH CDR2 having an amino acid sequence of SEQ ID NO:230; a VH CDR3 having an amino acid sequence of SEQ ID NO:231, wherein the ninth amino acid is H or Y; a VL CDR1 having an amino acid sequence of SEQ ID NO:232, wherein the fourth amino acid is N, R, or S, and the fifth amino acid is I or P; a VL CDR2 having an amino acid sequence of SEQ ID NO:233, wherein the first amino acid is F, H or Y; and a VL CDR3 having an amino acid sequence of SEQ ID NO:234.


In one aspect, provided herein is an antibody that binds CD8, comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:365, wherein the third amino acid is I or T; a VH CDR2 having an amino acid sequence of SEQ ID NO:366, wherein the seventh amino acid is D or I; and a VH CDR3 having an amino acid sequence of SEQ ID NO:367, wherein the ninth amino acid is H or Y. In one aspect, provided herein is an antibody that binds CD8, comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:368, wherein the fourth amino acid is D or G, and the fifth amino acid is K or T; a VL CDR2 having an amino acid sequence of SEQ ID NO:369; and a VL CDR3 having an amino acid sequence of SEQ ID NO:370, wherein the fifth amino acid is S or T and the eighth amino acid is S or T. In one aspect, provided herein is an antibody that binds CD8, comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:365, wherein the third amino acid is I or T; a VH CDR2 having an amino acid sequence of SEQ ID NO:366, wherein the seventh amino acid is D or I; a VH CDR3 having an amino acid sequence of SEQ ID NO:367, wherein the ninth amino acid is H or Y; a VL CDR1 having an amino acid sequence of SEQ ID NO:368, wherein the fourth amino acid is D or G, and the fifth amino acid is K or T; a VL CDR2 having an amino acid sequence of SEQ ID NO:369; and a VL CDR3 having an amino acid sequence of SEQ ID NO:370, wherein the fifth amino acid is S or T and the eighth amino acid is S or T.


In one aspect, provided herein is an antibody that binds CD8, comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:501, wherein the sixth amino acid is E or V; a VH CDR2 having an amino acid sequence of SEQ ID NO:502, wherein the fifth amino acid is N, S or T, the seventh amino acid is N or S, and the eighth amino acid is I or M; and a VH CDR3 having an amino acid sequence of SEQ ID NO:503, wherein the third amino acid is H or Y, and the twelfth amino acid is A or N. In one aspect, provided herein is an antibody that binds CD8, comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:504; a VL CDR2 having an amino acid sequence of SEQ ID NO:505; and a VL CDR3 having an amino acid sequence of SEQ ID NO:506, wherein the fifth amino acid is N or S, and the eighth amino acid is F or Y. In one aspect, provided herein is an antibody that binds CD8, comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:501, wherein the sixth amino acid is E or V; a VH CDR2 having an amino acid sequence of SEQ ID NO:502, wherein the fifth amino acid is N, S or T, the seventh amino acid is N or S, and the eighth amino acid is I or M; a VH CDR3 having an amino acid sequence of SEQ ID NO:503, wherein the third amino acid is H or Y, and the twelfth amino acid is A or N; a VL CDR1 having an amino acid sequence of SEQ ID NO:504; a VL CDR2 having an amino acid sequence of SEQ ID NO:505; and a VL CDR3 having an amino acid sequence of SEQ ID NO:506, wherein the fifth amino acid is N or S, and the eighth amino acid is F or Y.


In one aspect, provided herein is an antibody that binds CD8, comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:773, wherein the fifth amino acid is A or T, and the sixth amino acid is A or S; a VH CDR2 having an amino acid sequence of SEQ ID NO:774, wherein the first amino acid is I or V, the fourth amino acid is S or T, and the sixth amino acid is G, S or Y; and a VH CDR3 having an amino acid sequence of SEQ ID NO:775, wherein the first amino acid is A or S, the seventh amino acid is N or Y, the fourteenth amino acid is C or F, and the fifteenth amino acid is A or P. In one aspect, provided herein is an antibody that binds CD8, comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:776, wherein the first amino acid is A or D; a VL CDR2 having an amino acid sequence of SEQ ID NO:777, wherein the third amino acid is E or K; and a VL CDR3 having an amino acid sequence of SEQ ID NO:778, wherein the fifth amino acid is N or T, and the sixth amino acid is N, S or T. In one aspect, provided herein is an antibody that binds CD8, comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:773, wherein the fifth amino acid is A or T, and the sixth amino acid is A or S; a VH CDR2 having an amino acid sequence of SEQ ID NO:774, wherein the first amino acid is I or V, the fourth amino acid is S or T, and the sixth amino acid is G, S or Y; a VH CDR3 having an amino acid sequence of SEQ ID NO:775, wherein the first amino acid is A or S, the seventh amino acid is N or Y, the fourteenth amino acid is C or F, and the fifteenth amino acid is A or P; a VL CDR1 having an amino acid sequence of SEQ ID NO:776, wherein the first amino acid is A or D; a VL CDR2 having an amino acid sequence of SEQ ID NO:777, wherein the third amino acid is E or K; and a VL CDR3 having an amino acid sequence of SEQ ID NO:778, wherein the fifth amino acid is N or T, and the sixth amino acid is N, S or T.


In one aspect, provided herein is an antibody that binds CD8, comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:841; a VH CDR2 having an amino acid sequence of SEQ ID NO:842; and a VH CDR3 having an amino acid sequence of SEQ ID NO:843, wherein the tenth amino acid is H or Y. In one aspect, provided herein is an antibody that binds CD8, comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:844, wherein the sixth amino acid is A or D; a VL CDR2 having an amino acid sequence of SEQ ID NO:845; and a VL CDR3 having an amino acid sequence of SEQ ID NO:846, wherein the fourth amino acid is K or S, and the seventh amino acid is P or deleted. In one aspect, provided herein is an antibody that binds CD8, comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:841; a VH CDR2 having an amino acid sequence of SEQ ID NO:842; a VH CDR3 having an amino acid sequence of SEQ ID NO:843, wherein the tenth amino acid is H or Y; a VL CDR1 having an amino acid sequence of SEQ ID NO:844, wherein the sixth amino acid is A or D; a VL CDR2 having an amino acid sequence of SEQ ID NO:845; and a VL CDR3 having an amino acid sequence of SEQ ID NO:846, wherein the fourth amino acid is K or S, and the seventh amino acid is P or deleted.


In one aspect, provided herein is an antibody that binds CD8, comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:1011, wherein the fifth amino acid is S or T, the sixth amino acid is N, R or S, and the eighth amino acid is S or V; a VH CDR2 having an amino acid sequence of SEQ ID NO:1012, wherein the third amino acid is A, G or T, and the fourth amino acid is D or G; and a VH CDR3 having an amino acid sequence of SEQ ID NO:1013, wherein the second amino acid is K or R, the third amino acid is H, I or N, the fourth amino acid is N, S or Y, the fifth amino acid is F, G or Y, the sixth amino acid is D or Y, the seventh amino acid is F, N or S, the eighth amino acid is F, P or Y, the ninth amino acid is A, D or V, the tenth amino acid is A, G or F, and the twelfth amino acid is A or D. In one aspect, provided herein is an antibody that binds CD8, comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:1014, wherein the second amino acid is D or N, the fourth amino acid is D, G or N, and the sixth amino acid is D or V; a VL CDR2 having an amino acid sequence of SEQ ID NO:1015, wherein the first amino acid is S or W, and the second amino acid is A or T; and a VL CDR3 having an amino acid sequence of SEQ ID NO:1016. wherein the third amino acid is C or Y, the fourth amino acid is N or S, and the eighth amino acid is L or Y. In one aspect, provided herein is an antibody that binds CD8, comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:1011, wherein the fifth amino acid is S or T, the sixth amino acid is N, R or S, and the eighth amino acid is S or V; a VH CDR2 having an amino acid sequence of SEQ ID NO:1012, wherein the third amino acid is A, G or T, and the fourth amino acid is D or G; a VH CDR3 having an amino acid sequence of SEQ ID NO:1013, wherein the second amino acid is K or R, the third amino acid is H, I or N, the fourth amino acid is N, S or Y, the fifth amino acid is F, G or Y, the sixth amino acid is D or Y, the seventh amino acid is F, N or S, the eighth amino acid is F, P or Y, the ninth amino acid is A, D or V, the tenth amino acid is A, G or F, and the twelfth amino acid is A or D; a VL CDR1 having an amino acid sequence of SEQ ID NO:1014, wherein the second amino acid is D or N, the fourth amino acid is D, G or N, and the sixth amino acid is D or V; a VL CDR2 having an amino acid sequence of SEQ ID NO:1015, wherein the first amino acid is S or W, and the second amino acid is A or T; and a VL CDR3 having an amino acid sequence of SEQ ID NO:1016. wherein the third amino acid is C or Y, the fourth amino acid is N or S, and the eighth amino acid is L or Y.


In one aspect, provided herein is an antibody that binds CD8, comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:1045; a VH CDR2 having an amino acid sequence of SEQ ID NO:1046; and a VH CDR3 having an amino acid sequence of SEQ ID NO:1047, wherein the first amino acid is A or S. In one aspect, provided herein is an antibody that binds CD8, comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:1048; a VL CDR2 having an amino acid sequence of SEQ ID NO:1049; and a VL CDR3 having an amino acid sequence of SEQ ID NO:1050. In one aspect, provided herein is an antibody that binds CD8, comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:1045; a VH CDR2 having an amino acid sequence of SEQ ID NO:1046; a VH CDR3 having an amino acid sequence of SEQ ID NO:1047, wherein the first amino acid is A or S; a VL CDR1 having an amino acid sequence of SEQ ID NO:1048; a VL CDR2 having an amino acid sequence of SEQ ID NO: 1049; and a VL CDR3 having an amino acid sequence of SEQ ID NO:1050.


In one aspect, provided herein is an antibody that binds CD8, comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:1181, wherein the second amino acid is F or Y, the third amino acid is S or T, the fourth amino acid is F or L, and the eighth amino acid is A or W; a VH CDR2 having an amino acid sequence of SEQ ID NO:1182, wherein the second amino acid is D or W, the third amino acid is P or T, the fourth amino acid is D or S, the fifth amino acid is D or G, the sixth amino acid is S or T, and the seventh amino acid is F or deleted; and a VH CDR3 having an amino acid sequence of SEQ ID NO:1183, wherein the third amino acid is G or N, the fourth amino acid is D or N, the fifth amino acid is G or W, the sixth amino acid is D or Y, the seventh amino acid is F or R, the eighth amino acid is D or P, the ninth amino acid is A or W, the tenth amino acid is F or Y, the twelfth amino acid is A or D, and the thirteenth amino acid is V or Y. In one aspect, provided herein is an antibody that binds CD8, comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:1184, wherein the second amino acid is S or T, the third amino acid is I or L, the fourth amino acid is L or V, the fifth amino acid is H or Y, the seventh amino acid is D or N, and the ninth amino acid is K or N; a VL CDR2 having an amino acid sequence of SEQ ID NO:1185, wherein the first amino acid is K or L; and a VL CDR3 having an amino acid sequence of SEQ ID NO:1186, wherein the first amino acid is F or L, the third amino acid is A or G, the fourth amino acid is S or T, the sixth amino acid is A or F, and the eighth amino acid is F or H. In one aspect, provided herein is an antibody that binds CD8, comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:1181, wherein the second amino acid is F or Y, the third amino acid is S or T, the fourth amino acid is F or L, and the eighth amino acid is A or W; a VH CDR2 having an amino acid sequence of SEQ ID NO:1182, wherein the second amino acid is D or W, the third amino acid is P or T, the fourth amino acid is D or S, the fifth amino acid is D or G, the sixth amino acid is S or T, and the seventh amino acid is F or deleted; a VH CDR3 having an amino acid sequence of SEQ ID NO:1183, wherein the third amino acid is G or N, the fourth amino acid is D or N, the fifth amino acid is G or W, the sixth amino acid is D or Y, the seventh amino acid is F or R, the eighth amino acid is D or P, the ninth amino acid is A or W, the tenth amino acid is F or Y, the twelfth amino acid is A or D, and the thirteenth amino acid is V or Y; a VL CDR1 having an amino acid sequence of SEQ ID NO:1184, wherein the second amino acid is S or T, the third amino acid is I or L, the fourth amino acid is L or V, the fifth amino acid is H or Y, the seventh amino acid is D or N, and the ninth amino acid is K or N; a VL CDR2 having an amino acid sequence of SEQ ID NO:1185, wherein the first amino acid is K or L; and a VL CDR3 having an amino acid sequence of SEQ ID NO:1186, wherein the first amino acid is F or L, the third amino acid is A or G, the fourth amino acid is S or T, the sixth amino acid is A or F, and the eighth amino acid is F or H.


In one aspect, provided herein is an antibody that binds CD8, comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:1283; a VH CDR2 having an amino acid sequence of SEQ ID NO:1284; and a VH CDR3 having an amino acid sequence of SEQ ID NO:1285, wherein the first amino acid is A or T, the sixth amino acid is A or P, the ninth amino acid is H or R, and the fourteenth amino acid is D or V. In one aspect, provided herein is an antibody that binds CD8, comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:1286; a VL CDR2 having an amino acid sequence of SEQ ID NO:1287; and a VL CDR3 having an amino acid sequence of SEQ ID NO:1288, wherein the first amino acid is I or S. In one aspect, provided herein is an antibody that binds CD8, comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:1283; a VH CDR2 having an amino acid sequence of SEQ ID NO:1284; a VH CDR3 having an amino acid sequence of SEQ ID NO:1285, wherein the first amino acid is A or T, the sixth amino acid is A or P, the ninth amino acid is H or R, and the fourteenth amino acid is D or V; a VL CDR1 having an amino acid sequence of SEQ ID NO: 1286; a VL CDR2 having an amino acid sequence of SEQ ID NO:1287; and a VL CDR3 having an amino acid sequence of SEQ ID NO:1288, wherein the first amino acid is I or S.


In one aspect, provided herein is an antibody that binds CD8, comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:1385, wherein the fifth amino acid is N or S; a VH CDR2 having an amino acid sequence of SEQ ID NO:1386, wherein the seventh amino acid is K or R; and a VH CDR3 having an amino acid sequence of SEQ ID NO:1387, wherein the fourth amino acid is D or V. In one aspect, provided herein is an antibody that binds CD8, comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:1388; a VL CDR2 having an amino acid sequence of SEQ ID NO:1389; and a VL CDR3 having an amino acid sequence of SEQ ID NO:1390. In one aspect, provided herein is an antibody that binds CD8, comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:1385, wherein the fifth amino acid is N or S; a VH CDR2 having an amino acid sequence of SEQ ID NO:1386, wherein the seventh amino acid is K or R; a VH CDR3 having an amino acid sequence of SEQ ID NO:1387, wherein the fourth amino acid is D or V; a VL CDR1 having an amino acid sequence of SEQ ID NO:1388; a VL CDR2 having an amino acid sequence of SEQ ID NO:1389; and a VL CDR3 having an amino acid sequence of SEQ ID NO:1390.


In one aspect, provided herein is an antibody that binds CD8, comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:1419, wherein the third amino acid is S or T, the fourth amino acid is F or S, the fifth amino acid is A or T, the sixth amino acid is S or N, and the seventh amino acid is F, H or Y; a VH CDR2 having an amino acid sequence of SEQ ID NO:1420, wherein the fourth amino acid is F or G, the sixth amino acid is D or S, and the eighth amino acid is S or T; and a VH CDR3 having an amino acid sequence of SEQ ID NO:1421, wherein the third amino acid is E or H, the fourth amino acid is E or S, the fifth amino acid is A, F, P or Y, the sixth amino acid is D, G or S, the seventh amino acid is H or Y, the eighth amino acid is F, K, R, or Y, the ninth amino acid is D, P, S, or Y, the tenth amino acid is S, T, or Y, the eleventh amino acid is A or W, the twelfth amino acid is M or F, and the thirteenth amino acid is A, D or V. In one aspect, provided herein is an antibody that binds CD8, comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:1422, wherein the fifth amino acid is I or T; a VL CDR2 having an amino acid sequence of SEQ ID NO:1423; and a VL CDR3 having an amino acid sequence of SEQ ID NO:1424, wherein the fifth amino acid is S or T, the sixth amino acid is D or Y, and the eighth amino acid is F, L, or Y. In one aspect, provided herein is an antibody that binds CD8, comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:1419, wherein the third amino acid is S or T, the fourth amino acid is F or S, the fifth amino acid is A or T, the sixth amino acid is S or N, and the seventh amino acid is F, H or Y; a VH CDR2 having an amino acid sequence of SEQ ID NO:1420, wherein the fourth amino acid is F or G, the sixth amino acid is D or S, and the eighth amino acid is S or T; a VH CDR3 having an amino acid sequence of SEQ ID NO:1421, wherein the third amino acid is E or H, the fourth amino acid is E or S, the fifth amino acid is A, F, P or Y, the sixth amino acid is D, G or S, the seventh amino acid is H or Y, the eighth amino acid is F, K, R, or Y, the ninth amino acid is D, P, S, or Y, the tenth amino acid is S, T, or Y, the eleventh amino acid is A or W, the twelfth amino acid is M or F, and the thirteenth amino acid is A, D or V; a VL CDR1 having an amino acid sequence of SEQ ID NO:1422, wherein the fifth amino acid is I or T; a VL CDR2 having an amino acid sequence of SEQ ID NO:1423; and a VL CDR3 having an amino acid sequence of SEQ ID NO:1424, wherein the fifth amino acid is S or T, the sixth amino acid is D or Y, and the eighth amino acid is F, L, or Y.


In one aspect, provided herein is an antibody that binds CD8, comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:1759, wherein the third amino acid is S or T, the sixth amino acid is S or T, the seventh amino acid is A or Y, and the eighth amino acid is G or Y; a VH CDR2 having an amino acid sequence of SEQ ID NO:1760, wherein the second amino acid is D or N, the third amino acid is P or T, the fourth amino acid is F or H, the fifth amino acid is A or N, the seventh amino acid is E or N, and the eight amino acid is S or T; and a VH CDR3 having an amino acid sequence of SEQ ID NO:1761, wherein the second amino acid is R or S, the third amino acid is P or S, the fourth amino acid is G or N, the fifth amino acid is D or S, the sixth amino acid is N or Y, the seventh amino acid is D or Y, the eighth amino acid is G or V, the ninth amino acid is G or S, the tenth amino acid is H or T, and the eleventh amino acid is P or W. In one aspect, provided herein is an antibody that binds CD8, comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:1762, wherein the second amino acid is D or N, the fourth amino acid is N or R, the fifth amino acid is P or V, and the sixth amino acid is W or Y; a VL CDR2 having an amino acid sequence of SEQ ID NO:1763, wherein the first amino acid is K or Y, and the second amino acid is A or T; and a VL CDR3 having an amino acid sequence of SEQ ID NO:1764, wherein the first amino acid is D or G, the fourth amino acid is N or Q, the fifth amino acid is S or T, the sixth amino acid is F or L, and the eight amino acid is F or Y. In one aspect, provided herein is an antibody that binds CD8, comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:1759, wherein the third amino acid is S or T, the sixth amino acid is S or T, the seventh amino acid is A or Y, and the eighth amino acid is G or Y; a VH CDR2 having an amino acid sequence of SEQ ID NO:1760, wherein the second amino acid is D or N, the third amino acid is P or T, the fourth amino acid is F or H, the fifth amino acid is A or N, the seventh amino acid is E or N, and the eight amino acid is S or T; a VH CDR3 having an amino acid sequence of SEQ ID NO:1761, wherein the second amino acid is R or S, the third amino acid is P or S, the fourth amino acid is G or N, the fifth amino acid is D or S, the sixth amino acid is N or Y, the seventh amino acid is D or Y, the eighth amino acid is G or V, the ninth amino acid is G or S, the tenth amino acid is H or T, and the eleventh amino acid is P or W; a VL CDR1 having an amino acid sequence of SEQ ID NO:1762, wherein the second amino acid is D or N, the fourth amino acid is N or R, the fifth amino acid is P or V, and the sixth amino acid is W or Y; a VL CDR2 having an amino acid sequence of SEQ ID NO:1763, wherein the first amino acid is K or Y, and the second amino acid is A or T; and a VL CDR3 having an amino acid sequence of SEQ ID NO:1764, wherein the first amino acid is D or G, the fourth amino acid is N or Q, the fifth amino acid is S or T, the sixth amino acid is F or L, and the eight amino acid is F or Y.


In one aspect, provided herein is an antibody that binds CD8, comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:1827, wherein the third amino acid is K or T; a VH CDR2 having an amino acid sequence of SEQ ID NO:1828; and a VH CDR3 having an amino acid sequence of SEQ ID NO:1829. In one aspect, provided herein is an antibody that binds CD8, comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:1830; a VL CDR2 having an amino acid sequence of SEQ ID NO:1831, wherein the second amino acid is A or T; and a VL CDR3 having an amino acid sequence of SEQ ID NO:1832, wherein the fifth amino acid is I or S. In one aspect, provided herein is an antibody that binds CD8, comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:1827, wherein the third amino acid is K or T; a VH CDR2 having an amino acid sequence of SEQ ID NO:1828; and a VH CDR3 having an amino acid sequence of SEQ ID NO:1829; a VL CDR1 having an amino acid sequence of SEQ ID NO:1830; a VL CDR2 having an amino acid sequence of SEQ ID NO:1831, wherein the second amino acid is A or T; and a VL CDR3 having an amino acid sequence of SEQ ID NO:1832, wherein the fifth amino acid is I or S.


In another aspect, provided herein is an antibody that competes for binding to CD8 with any of the CD8 antibodies described herein. In another aspect, provided herein is an antibody that binds to the same epitope as any of the CD8 antibodies described herein. In another aspect, provided is a CD8 antibody that binds an epitope on CD8 that overlaps with the epitope on CD8 bound by a CD8 antibody described herein.


In one aspect, provided is an antibody that competes for binding to CD8 with a CD8 reference antibody. In another aspect, provided is a CD8 antibody that binds to the same CD8 epitope as a CD8 reference antibody. In another aspect, provided is a CD8 antibody that binds an epitope on CD8 that overlaps with the epitope on CD8 bound by a CD8 reference antibody. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:31; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:32. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:65; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:66. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:99; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:100. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:133; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:134. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:167; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:168. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:201; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:202. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:235; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:236. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:269; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:270. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:303; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:304. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:337; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:338. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:371; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:372. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:405; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:406. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:439; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:440. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:473; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:474. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:507; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:508. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:541; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:542. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:575; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:576. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:609; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:610. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:643; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:644. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:677; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:678. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:711; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:712. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:745; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:746. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:779; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:780. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:813; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:814. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:847; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:848. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:881; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:882. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:915; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:916. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:949; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:950. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:983; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:984. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1017; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1018. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1051; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1052. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1085; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1086. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1119; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1120. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1153; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1154. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1187; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1188. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1221; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1222. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1255; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1256. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1289; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1290. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1323; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1324. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1357; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1358. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1391; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1392. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1425; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1426. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1459; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1460. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1493; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1494. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1527; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1528. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1561; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1562. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1595; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1596. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1629; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1630. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1663; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1664. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1697; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1698. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1731; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1732. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1765; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1766. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1799; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1800. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1833; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1834. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1867; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1868. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1901; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1902. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1935; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1936. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1969; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1970. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2003; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2004. In another aspect, provided herein is an antibody that binds CD8. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2037; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2038. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2071; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2072. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2105; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2106. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2139; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2140. In one embodiment, the CD8 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2173; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2174.


In another aspect, provided herein is a multispecific antibody that binds CD8. In some embodiments, the multispecific antibody is a bispecific antibody. In some embodiments, the multispecific antibody is a trispecific antibody. In some embodiments, the multispecific antibody is a quadraspecific antibody. In one embodiment, the multispecific CD8 antibody comprises: (a) a first binding domain that binds CD8, and (b) a second binding domain that binds to a second target. In one embodiment, the multispecific CD8 antibody comprises: (a) a first binding domain that binds CD8, and (b) a second binding domain that binds to a second target, and (c) a third binding domain that binds to a third target. In one embodiment, the multispecific CD8 antibody comprises: (a) a first binding domain that binds CD8, and (b) a second binding domain that binds to a second target, (c) a third binding domain that binds to a third target, and (d) a fourth binding domain that binds to a fourth target.


In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:31; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:32. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:65; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:66. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:99; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:100. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:133; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:134. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:167; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:168. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:201; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:202. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:235; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:236. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:269; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:270. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:303; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:304. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:337; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:338. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:371; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:372. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:405; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:406. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:439; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:440. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:473; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:474. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:507; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:508. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:541; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:542. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:575; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:576. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:609; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:610. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:643; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:644. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:677; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:678. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:711; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:712. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:745; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:746. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:779; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:780. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:813; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:814. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:847; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:848. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:881; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:882. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:915; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:916. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:949; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:950. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:983; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:984. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1017; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1018. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1051; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1052. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1085; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1086. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1119; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1120. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1153; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1154. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1187; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1188. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1221; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1222. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1255; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1256. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1289; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1290. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1323; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1324. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1357; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1358. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1391; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1392. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1425; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1426. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1459; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1460. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1493; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1494. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1527; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1528. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1561; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1562. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1595; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1596. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1629; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1630. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1663; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1664. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1697; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1698. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1731; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1732. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1765; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1766. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1799; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1800. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1833; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1834. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1867; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1868. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1901; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1902. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1935; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1936. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1969; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1970. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2003; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2004. In another aspect, provided herein is an antibody that binds CD8. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2037; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2038. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2071; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2072. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2105; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2106. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2139; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2140. In one embodiment, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2173; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2174.


In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the first binding domain that binds CD8 are according to the Kabat numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the first binding domain that binds CD8 are according to the Chothia numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the first binding domain that binds CD8 are according to the AbM numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the first binding domain that binds CD8 are according to the Contact numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the first binding domain that binds CD8 are according to the IMGT numbering system.


In some embodiments, the first binding domain binds a CD8 antigen. In some embodiments, the first binding domain binds a CD8 epitope. In some embodiments, the first binding domain specifically binds to CD8. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the first binding domain form a binding site for an antigen of the CD8. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the first binding domain form a binding site for an epitope of the CD8. In some embodiments, the CD8 is present on the surface of a T cell. In some embodiments, the first binding domain binds to CD8α. In some embodiments, the first binding domain binds a CD8α antigen. In some embodiments, the first binding domain that binds a CD8α epitope. In some embodiments, the first binding domain specifically binds to CD8α. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the first binding domain form a binding site for an antigen of the CD8α. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the first binding domain form a binding site for an epitope of the CD8α. In some embodiments, the CD8α is present on the surface of a T cell. In some embodiments, the first binding domain binds to CD8β. In some embodiments, the first binding domain binds a CD8β antigen. In some embodiments, the first binding domain that binds a CD8β epitope. In some embodiments, the first binding domain specifically binds to CD8β. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the first binding domain form a binding site for an antigen of the CD8β. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the first binding domain form a binding site for an epitope of the CD8β. In some embodiments, the CD8β is present on the surface of a T cell. In some embodiments, the first binding domain binds at the interface of CD8α and CD8β. In some embodiments, the first binding domain binds an antigen at the interface of CD8α and CD8β. In some embodiments, first binding domain binds an epitope at the interface of CD8α and CD8β. In some embodiments, the first binding domain specifically binds at the interface of CD8α and CD8β. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the first binding domain form a binding site for an antigen at the interface of CD8α and CD8β. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the first binding domain form a binding site for an epitope at the interface of CD8α and CD8β. In some embodiments, the interface of CD8α and CD8β is present on the surface of a T cell.


In some embodiments of the multispecific CD8 antibodies provided herein, the second target is not a CD8 antigen. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is not a CD8 antigen. In some embodiments of the multispecific CD8 antibodies provided herein, the fourth target is not a CD8 antigen. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is not a CD8 antigen, and the third target is not a CD8 antigen. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is not a CD8 antigen, and the fourth target is not a CD8 antigen. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is not a CD8 antigen, and the fourth target is not a CD8 antigen. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is not a CD8 antigen, the third target is not a CD8 antigen, and the fourth target is not a CD8 antigen. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is not a CD8 epitope. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is not a CD8 epitope. In some embodiments of the multispecific CD8 antibodies provided herein, the fourth target is not a CD8 epitope. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is not a CD8 epitope, and the third target is not a CD8 epitope. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is not a CD8 epitope, and the fourth target is not a CD8 epitope. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is not a CD8 epitope, and the fourth target is not a CD8 epitope. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is not a CD8 epitope, the third target is not a CD8 epitope, and the fourth target is not a CD8 epitope.


In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is a T cell receptor (TCR) complex. As used herein, “TCR complex” refers to a known TCR complex comprising TCRα and TCRβ chains, CD3ε, CD3γ, CD3δ, and CD3ζ molecules. In certain embodiments, TCRα and TCRβ chains are replaced by TCRγ and TCRδ chains. The amino acid sequences of the various proteins forming the TCR complex are known. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD3. In some embodiments, CD3 comprises CD3ε. In some embodiments, CD3 comprises CD3γ. In some embodiments, CD3 comprises CD3δ. In some embodiments, CD3 comprises CD3ζ. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD3ε. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD3γ. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD3δ. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD3ζ. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is a TCRα chain. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is a TCRβ chain. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is a TCRγ chain. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is a TCRδ chain. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is a T cell costimulatory molecule. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD28. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CTLA4. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is ICOS. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is 4-1BB. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is GITR. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD27. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is OX40. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD40L. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is HVEM. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is Galectin-9. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is TIM-1. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is LFA1. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD2. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is PD1. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is a TCR complex. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is CD3. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is CD3ε. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is CD3γ. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is CD3δ. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is CD3ζ. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is a TCRα chain. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is a TCRβ chain. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is a TCRγ chain. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is a TCRδ chain. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is a T cell costimulatory molecule. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is CD28. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is CTLA4. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is ICOS. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is 4-1BB. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is GITR. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is CD27. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is OX40. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is CD40L. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is HVEM. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is Galectin-9. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is TIM-1. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is LFA1. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is CD2. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is PD1. In some embodiments of the multispecific CD8 antibodies provided herein, the fourth target is a TCR complex. In some embodiments of the multispecific CD8 antibodies provided herein, the fourth target is CD3. In some embodiments of the multispecific CD8 antibodies provided herein, the fourth target is CD3ε. In some embodiments of the multispecific CD8 antibodies provided herein, the fourth target is CD3γ. In some embodiments of the multispecific CD8 antibodies provided herein, the fourth target is CD3δ. In some embodiments of the multispecific CD8 antibodies provided herein, the fourth target is CD3ζ. In some embodiments of the multispecific CD8 antibodies provided herein, the fourth target is a TCRα chain. In some embodiments of the multispecific CD8 antibodies provided herein, the fourth target is a TCRβ chain. In some embodiments of the multispecific CD8 antibodies provided herein, the fourth target is a TCRγ chain. In some embodiments of the multispecific CD8 antibodies provided herein, the fourth target is a TCRδ chain. In some embodiments of the multispecific CD8 antibodies provided herein, the fourth target is a T cell costimulatory molecule. In some embodiments of the multispecific CD8 antibodies provided herein, the fourth target is CD28. In some embodiments of the multispecific CD8 antibodies provided herein, the fourth target is CTLA4. In some embodiments of the multispecific CD8 antibodies provided herein, the fourth target is ICOS. In some embodiments of the multispecific CD8 antibodies provided herein, the fourth target is 4-1BB. In some embodiments of the multispecific CD8 antibodies provided herein, the fourth target is GITR. In some embodiments of the multispecific CD8 antibodies provided herein, the fourth target is CD27. In some embodiments of the multispecific CD8 antibodies provided herein, the fourth target is OX40. In some embodiments of the multispecific CD8 antibodies provided herein, the fourth target is CD40L. In some embodiments of the multispecific CD8 antibodies provided herein, the fourth target is HVEM. In some embodiments of the multispecific CD8 antibodies provided herein, the fourth target is Galectin-9. In some embodiments of the multispecific CD8 antibodies provided herein, the fourth target is TIM-1. In some embodiments of the multispecific CD8 antibodies provided herein, the fourth target is LFA1. In some embodiments of the multispecific CD8 antibodies provided herein, the fourth target is CD2. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is HVEM. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is Galectin-9. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is TIM-1. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is LFA1. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD2.


In some embodiments of the multispecific CD8 antibodies provided herein, the fourth target is PD1. In some embodiments, the second target is CD4. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is CD3. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is TCRα chain. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is a TCRβ chain. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is a TCRγ chain. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is a TCRδ chain. In some embodiments of the multispecific CD8 antibodies provided herein, the third target is CD28. In some embodiments of the multispecific CD8 antibodies provided herein, the fourth target is CD28.


In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, and the third target is a TCR complex. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, and the third target is CD3. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, and the third target is CD3ε. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, and the third target is CD3γ. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, and the third target is CD3δ. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, and the third target is CD3ζ. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, and the third target is a TCRα chain. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, and the third target is a TCRβ chain. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, and the third target is a TCRγ chain.


In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, and the third target is a T cell costimulatory molecule. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, and the third target is CD28. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, and the third target is CTLA4. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, and the third target is ICOS. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, and the third target is 4-1BB. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, and the third target is GITR. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, and the third target is CD27. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, and the third target is OX40. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, and the third target is CD40L. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, and the third target is HVEM. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, and the third target is Galectin-9. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, and the third target is TIM-1. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, and the third target is LFA1. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, and the third target is CD2. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, and the third target is PD1.


In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, the third target is a TCR complex, and the fourth target is a T cell costimulatory molecule. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, the third target is CD3, and the fourth target is a T cell costimulatory molecule. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, the third target is CD3ε, and the fourth target is a T cell costimulatory molecule. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, the third target is CD3γ, and the fourth target is a T cell costimulatory molecule. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, the third target is CD3δ, and the fourth target is a T cell costimulatory molecule. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, the third target is CD3ζ, and the fourth target is a T cell costimulatory molecule. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, the third target is a TCRα chain, and the fourth target is a T cell costimulatory molecule. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, the third target is a TCRβ chain, and the fourth target is a T cell costimulatory molecule. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD4, the third target is a TCRγ chain, and the fourth target is a T cell costimulatory molecule. In certain embodiments, the T cell costimulatory molecule is CD28. In certain embodiments, the T cell costimulatory molecule is CTLA4. In certain embodiments, the T cell costimulatory molecule is ICOS. In certain embodiments, the T cell costimulatory molecule is 4-1BB. In certain embodiments, the T cell costimulatory molecule is GITR. In certain embodiments, the T cell costimulatory molecule is CD27. In certain embodiments, the T cell costimulatory molecule is OX40. In certain embodiments, the T cell costimulatory molecule is CD40L. In certain embodiments, the T cell costimulatory molecule is HVEM. In certain embodiments, the T cell costimulatory molecule is Galectin-9. In certain embodiments, the T cell costimulatory molecule is TIM-1. In certain embodiments, the T cell costimulatory molecule is LFA1. In certain embodiments, the T cell costimulatory molecule is CD2. In certain embodiments, the T cell costimulatory molecule is PD1.


In some embodiments of the multispecific CD8 antibodies provided herein, the second target is a TCR complex, and the third target is a T cell costimulatory molecule. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD3, and the third target is a T cell costimulatory molecule. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD3ε, and the third target is a T cell costimulatory molecule. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD3γ, and the third target is a T cell costimulatory molecule. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD3δ, and the third target is a T cell costimulatory molecule. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is CD3ζ, and the third target is a T cell costimulatory molecule. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is a TCRα chain, and the third target is a T cell costimulatory molecule. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is a TCRβ chain, and the third target is a T cell costimulatory molecule. In some embodiments of the multispecific CD8 antibodies provided herein, the second target is a TCRγ chain, and the third target is a T cell costimulatory molecule. In certain embodiments, the T cell costimulatory molecule is CD28. In certain embodiments, the T cell costimulatory molecule is CTLA4. In certain embodiments, the T cell costimulatory molecule is ICOS. In certain embodiments, the T cell costimulatory molecule is 4-1BB. In certain embodiments, the T cell costimulatory molecule is GITR. In certain embodiments, the T cell costimulatory molecule is CD27. In certain embodiments, the T cell costimulatory molecule is OX40. In certain embodiments, the T cell costimulatory molecule is CD40L. In certain embodiments, the T cell costimulatory molecule is HVEM. In certain embodiments, the T cell costimulatory molecule is Galectin-9. In certain embodiments, the T cell costimulatory molecule is TIM-1. In certain embodiments, the T cell costimulatory molecule is LFA1. In certain embodiments, the T cell costimulatory molecule is CD2. In certain embodiments, the T cell costimulatory molecule is PD1.


In a specific embodiment, the target is from a mammal. In a specific embodiment, the target is from a rat. In a specific embodiment, the target is from a mouse. In a specific embodiment, the target is from a primate. In a specific embodiment, the target is from a human.


In specific embodiments, provided is a multispecific antibody comprising a CD8 antibody provided herein in a knob-in-hole format. In specific embodiments, provided is a bispecific antibody comprising a CD8 antibody provided herein in a knob-in-hole format. In specific embodiments, provided is a trispecific antibody comprising a CD8 antibody provided herein in a knob-in-hole format. In specific embodiments, provided is a quadraspecific antibody comprising a CD8 antibody provided herein in a knob-in-hole format. Other specificities can be added to an antibody in knob-in-hole format using methods well known in the art (e.g., adding an scFv to the N-terminus or C-terminus). In addition, other formats and methods of making multispecific antibodies are also known in the art and contemplated. In some embodiments, a CD8 antibody provided herein is comprised in a bispecific antibody. In some embodiments, a CD8 antibody provided herein is comprised in a trispecific antibody. In some embodiments, a CD8 antibody provided herein is comprised in a quadraspecific antibody. In some embodiments, a CD8 bispecific antibody provided herein is comprised in a multispecific antibody.


In certain embodiments, a multispecific antibody provided herein comprises a first binding domain comprising a CD8 antibody provided herein that binds to a first CD8 epitope, and a second binding domain that binds to a second epitope, wherein the first CD8 epitope and the second epitope are not the same. In certain embodiments, a bispecific antibody provided herein comprises a first binding domain comprising a CD8 antibody provided herein that binds to a first CD8 epitope, and a second binding domain that binds to a second epitope, wherein the first CD8 epitope and the second epitope are not the same. In certain embodiments, a trispecific antibody provided herein comprises a first binding domain comprising a CD8 antibody provided herein that binds to a first CD8 epitope, a second binding domain that binds to a second epitope, and a third binding domain that binds to a third epitope, wherein the first CD8 epitope, the second epitope, and the third epitope are not the same. In certain embodiments, a quadraspecific antibody provided herein comprises a first binding domain comprising a CD8 antibody provided herein that binds to a first CD8 epitope, a second binding domain that binds to a second epitope, a third binding domain that binds to a third epitope, and a fourth binding domain that binds to a fourth epitope, wherein the first CD8 epitope, the second epitope, the third epitope, and the fourth epitope are not the same. In certain embodiments, a multispecific antibody provided herein comprises a first binding domain comprising a CD8 antibody provided herein that binds to a first CD8 antigen, and a second binding domain that binds to a second antigen, wherein the first CD8 antigen and the second antigen are not the same. In certain embodiments, a bispecific antibody provided herein comprises a first binding domain comprising a CD8 antibody provided herein that binds to a first CD8 antigen, and a second binding domain that binds to a second antigen, wherein the first CD8 antigen and the second antigen are not the same. In certain embodiments, a trispecific antibody provided herein comprises a first binding domain comprising a CD8 antibody provided herein that binds to a first CD8 antigen, a second binding domain that binds to a second antigen, and a third binding domain that binds to a third antigen, wherein the first CD8 antigen, the second antigen, and the third antigen are not the same. In certain embodiments, a quadraspecific antibody provided herein comprises a first binding domain comprising a CD8 antibody provided herein that binds to a first CD8 antigen, a second binding domain that binds to a second antigen, a third binding domain that binds to a third antigen, and a fourth binding domain that binds to a fourth antigen, wherein the first CD8 antigen, the second antigen, the third antigen, and the fourth antigen are not the same. In a specific embodiment, a CD8 antibody, or antigen binding fragment thereof, provided herein specifically binds to CD8.


In some embodiments, the multispecific antibody comprises heavy chain variable regions and light chain variable region. In some embodiments, the first binding domain comprises a heavy chain variable region and a light chain variable region. In some embodiments, the second binding domain comprises a heavy chain variable region and a light chain variable region. In some embodiments, the first binding domain comprises a heavy chain variable region and a light chain variable region, and the second binding domain comprises a heavy chain variable region and a light chain variable region. In a some embodiments, the CD8 antibody is not a single domain antibody or nanobody. In some embodiments, the third binding domain comprises a heavy chain variable region and a light chain variable region. In some embodiments, the fourth binding domain comprises a heavy chain variable region and a light chain variable region.


In certain embodiments, the CD8 multispecific antibodies or antigen binding fragments thereof bind to a first epitope located on CD8 and a second epitope of a second target antigen. In some embodiments, provided herein is a multispecific antibody comprising: (a) a first binding domain that binds to a CD8 antigen, and (b) a second binding domain that binds to a second target antigen. In some embodiments, provided herein is a multispecific antibody comprising: (a) a first binding domain that specifically binds to a CD8 antigen, and (b) a second binding domain that specifically binds to a second target antigen. In some embodiments, provided herein is a multispecific antibody comprising: (a) a first binding domain that binds to a first epitope on a CD8 antigen, and (b) a second binding domain that binds to a second epitope on a second target antigen. In some embodiments, provided herein is a multispecific antibody comprising: (a) a first binding domain that specifically binds to a first epitope on a CD8 antigen, and (b) a second binding domain that specifically binds to a second epitope on a second target antigen.


In specific embodiments, the CD8 antigen is on the surface of a T cell. In certain embodiments, the second target antigen is not CD8. The binding of the CD8 multispecific antibody to CD8 present on the surface of the T cell, and the binding of the second target antigen present on the surface of the second target cell can, for example, result in the killing of the second target cell. In other embodiment, the binding of the CD8 multispecific antibody to CD8 present on the surface of the T cell, and the binding of a second target antigen can, for example, result in the activation of the T cell.


In one aspect, provided herein is an antibody that binds to CD4. In some embodiments, provided herein is an antibody that binds to a CD4 antigen. In some embodiments, provided herein is an antibody that binds to a CD4 epitope.


In some embodiments, the antibody comprises a heavy chain variable region and a light chain variable region. In a some embodiments, the CD4 antibody is not a single domain antibody or nanobody. In some embodiments, the CD4 antibody is a humanized antibody. In some embodiments, the CD4 antibody is a fully human antibody.


In certain embodiments, provided herein is a CD4 antibody comprising a VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and/or VL CDR3 of any one of the antibodies described herein. In some embodiments, provided herein is a CD4 antibody comprising a VH region of any one of the antibodies described herein. In some embodiments, provided herein is a CD4 antibody comprising a VL region of any one of the antibodies described herein. In some embodiments, provided herein is a CD4 antibody comprising a VH region of any one of the antibodies described herein, and a VL region of any one of the antibodies described herein. In some embodiments, provided herein is a CD4 antibody comprising a VH CDR1, VH CDR2, and VH CDR3 of any one of the antibodies described herein. In some embodiments, provided herein is a CD4 antibody comprising a VL CDR1, VL CDR2, and VL CDR3 of any one of the antibodies described herein. In some embodiments, provided herein is a CD4 antibody comprising a VH CDR1, VH CDR2, and VH CDR3 of any one of the antibodies described herein; and a VL CDR1, VL CDR2, and VL CDR3 of any one of the antibodies described herein. Representative VH and VL amino acid sequences, including VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 amino acid sequences, of CD4 antibodies provided herein are provided in Tables 11-16.


In certain embodiments, provided herein is a CD4 multispecific antibody comprising a binding domain that binds to CD4 having a VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and/or VL CDR3 of any one of the antibodies described herein. In some embodiments, provided herein is a CD4 multispecific antibody comprising a binding domain that binds to CD4 having a VH region of any one of the antibodies described herein. In some embodiments, provided herein is a CD4 multispecific antibody comprising a binding domain that binds to CD4 having a VL region of any one of the antibodies described herein. In some embodiments, provided herein is a CD4 multispecific antibody comprising a binding domain that binds to CD4 having a VH region of any one of the antibodies described herein, and a VL region of any one of the antibodies described herein. In some embodiments, provided herein is a CD4 multispecific antibody comprising a binding domain that binds to CD4 having a VH CDR1, VH CDR2, and VH CDR3 of any one of the antibodies described. In some embodiments, provided herein is a CD4 multispecific antibody comprising a binding domain that binds to CD4 having a VL CDR1, VL CDR2, and VL CDR3 of any one of the antibodies described herein. In some embodiments, provided herein is a CD4 multispecific antibody comprising a binding domain that binds to CD4 having a VH CDR1, VH CDR2, and VH CDR3 of any one of the antibodies described herein; and a VL CDR1, VL CDR2, and VL CDR3 of any one of the antibodies described herein. In certain embodiments, the CD4 antibody is a bispecific antibody. In certain embodiments, the CD4 antibody is a trispecific antibody. In certain embodiments, the CD4 antibody is a quadraspecific antibody.


In some embodiments, the antibody specifically binds CD4. In other embodiments, the CD4 is present on the surface of a T cell.


In some embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In other embodiments, the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody. In some embodiments, the antibody is a bispecific antibody. In some embodiments, the antibody is a trispecific antibody. In some embodiments, the antibody is a quadraspecific antibody. In certain embodiments, the antibody is multivalent. In other embodiments, the antibody is capable of binding at least three antigens. In some embodiments, the antibody is capable of binding at least four antigens. In some embodiments, the antibody is capable of binding at least five antigens.


In certain embodiments, provided is a CD4 antibody that is an intact antibody. In other embodiments, provided is a CD4 antibody is an antigen binding fragment of the CD4 antibody. In some embodiments, the antigen binding fragment of the CD4 antibody is a functional fragment.


In some embodiments, the antigen binding fragment is a diabody. In some embodiments, the antigen binding fragment is a Fab. In some embodiments, the antigen binding fragment is a Fab′. In some embodiments, the antigen binding fragment is a F(ab′)2. In some embodiments, the antigen binding fragment is a Fv fragment. In some embodiments, the antigen binding fragment is a disulfide stabilized Fv fragment (dsFv). In some embodiments, the antigen binding fragment is a (dsFv)2. In some embodiments, the antigen binding fragment is a bispecific dsFv (dsFv-dsFv′). In some embodiments, the antigen binding fragment is a disulfide stabilized diabody (ds diabody). In some embodiments, the antigen binding fragment is a single-chain antibody molecule (scFv). In some embodiments, the antigen binding fragment is a single domain antibody (sdAb). In some embodiments, the antigen binding fragment is an scFv dimer (bivalent diabody). In some embodiments, the antigen binding fragment is a multispecific antibody formed from a portion of an antibody comprising one or more CDRs. In some embodiments, the antigen binding fragment is a camelized single domain antibody. In some embodiments, the antigen binding fragment is a nanobody. In some embodiments, the antigen binding fragment is a domain antibody. In some embodiments, the antigen binding fragment is a bivalent domain antibody. In some embodiments, the antigen binding fragment is an antibody fragment that binds to an antigen but does not comprise a complete antibody structure.


In specific embodiments, the CD4 antibody comprises a VH region and a VL region. In some embodiments, the CD4 antibody is a single chain antibody. In some embodiments, the CD4 antibody is a single domain antibody. In some embodiments, the CD4 antibody is a nanobody. In certain embodiments, the CD4 antibody is a VHH antibody. In certain embodiments, the CD4 antibody is a llama antibody. In some embodiments, the CD4 antibody is not a single chain antibody. In some embodiments, the CD4 antibody is not a single domain antibody. In some embodiments, the CD4 antibody is not a nanobody. In certain embodiments, the CD4 antibody is not a VHH antibody. In certain embodiments, the CD4 antibody is not a llama antibody. In some embodiments, the CD4 antibody is a multispecific antibody In other embodiments, the CD4 antibody is a bispecific antibody. In other embodiments, the CD4 antibody is a trispecific antibody. In other embodiments, the CD4 antibody is a quadraspecific antibody. In certain embodiments, the multispecific antibody comprises an antigen binding fragment of a CD4 antibody provided herein. In other embodiments, the bispecific antibody comprises an antigen binding fragment of a CD4 antibody provided herein. In other embodiments, the trispecific antibody comprises an antigen binding fragment of a CD4 antibody provided herein. In other embodiments, the quadraspecific antibody comprises an antigen binding fragment of a CD4 antibody provided herein. In In certain embodiments, the CD4 antibody activates T cells. In other embodiments, the CD4 antibody is an antagonistic antibody. In certain embodiments, the CD4 antibody inactivates T cells. In some embodiments, the CD4 antibody blocks activation of T cells. In some embodiments, the CD4 antibody modulates the activity of T cells. In some embodiments, the CD4 antibody neither activates or inactivates the activity of T cells. In specific embodiments, the T cells are human T cells.


In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences are according to the Kabat numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences are according to the Chothia numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences are according to the Exemplary numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences are according to the Contact numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences are according to the IMGT numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences are according to the AbM numbering system. Exemplary sets of 6 CDRs (VH CDR1-3 and VL CDR1-3) of certain antibody embodiments are provided herein. Other sets of CDRs are contemplated and within the scope of the antibody embodiments provided herein.


In one aspect, provided herein is an antibody that binds CD4. In one embodiment, provided is an antibody having a VH CDR1, VH CDR2 and a VH CDR3 of a CD4 antibody provided herein. In one embodiment, provided is an antibody having a VL CDR1, VL CDR2 and a VL CDR3 of a CD4 antibody provided herein. In one embodiment, provided is an antibody having a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of a CD4 antibody provided herein. In one embodiment, provided is an antibody having a VH of a CD4 antibody provided herein. In one embodiment, provided is an antibody having a VL of a CD4 antibody provided herein. In one embodiment, provided is an antibody having a VH and a VL of a CD4 antibody provided herein. In one embodiment, provided is an antibody having a heavy chain of a CD4 antibody provided herein. In one embodiment, provided is an antibody having a light chain of a CD4 antibody provided herein. In one embodiment, provided is an antibody having a heavy chain and a light chain of a CD4 antibody provided herein.


In another aspect, provided herein is an antibody that binds CD4. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2207. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2208. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2207; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2208. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2241. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2242. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2241; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2242. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2275. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2276. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2275; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2276. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2309. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2310. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2309; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2310. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2343. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2344. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2343; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2344. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2377. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2378. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2377; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2378. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2411. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2412. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2411; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2412. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2445. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2446. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2445; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2446. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2479. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2480. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2479; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2480. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2513. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2514. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2513; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2514. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2547. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2548. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2547; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2548. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2581. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2582. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2581; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2582. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2615. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2616. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2615; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2616. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2649. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2650. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2649; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2650. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2683. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2684. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2683; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2684. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2717. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2718. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2717; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2718. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2751. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2752. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2751; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2752. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2785. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2786. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2785; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2786. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2819. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2820. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2819; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2820. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2853. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2854. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2853; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2854. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2887. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2888. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2887; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2888. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2921. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2922. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2921; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2922. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2955. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2956. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2955; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2956. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2989. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2990. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2989; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2990. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3023. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3024. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3023; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3024. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3057. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3058. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3057; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3058. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3091. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3092. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3091; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3092. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3125. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3126. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3125; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3126. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3159. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3160. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3159; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3160. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3193. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3194. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3193; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3194. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3227. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3228. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3227; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3228. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3261. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3262. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3261; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3262. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3295. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3296. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3295; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3296. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3329. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3330. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3329; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3330. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3363. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3364. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3363; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3364. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3397. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3398. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3397; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3398. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3431. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3432. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3431; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3432. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3465. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3466. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3465; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3466. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3499. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3500. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3499; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3500. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3533. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3534. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3533; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3534. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3567. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3568. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3567; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3568. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3601. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3602. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3601; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3602. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3635. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3636. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3635; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3636. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3669. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3670. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3669; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3670. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3703. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3704. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3703; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3704. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3737. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3738. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3737; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3738. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3771. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3772. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3771; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3772. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3805. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3806. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3805; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3806. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3839. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3840. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3839; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3840. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3873. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3874. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3873; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3874. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3907. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3908. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3907; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3908. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3941. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3942. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3941; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3942. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3975. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3976. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3975; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3976. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4009. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4010. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4009; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4010. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4043. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4044. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4043; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4044. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4077. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4078. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4077; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4078. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4111. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4112. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4111; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4112. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4145. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4146. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4145; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4146. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4179. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4180. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4179; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4180. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4213. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4214. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4213; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4214. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4247. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4248. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4247; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4248. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4281. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4282. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4281; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4282. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4315. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4316. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4315; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4316. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4349. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4350. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4349; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4350. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4383. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4384. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4383; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4384. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4417. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4418. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4417; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4418. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4451. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4452. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4451; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4452. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4485. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4486. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4485; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4486. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4519. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4520. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4519; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4520. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4553. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4554. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4553; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4554. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4587. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4588. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4587; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4588. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4621. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4622. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4621; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4622. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4655. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4656. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4655; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4656. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4689. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4690. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4689; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4690. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4723. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4724. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4723; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4724. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4757. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4758. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4757; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4758. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4791. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4792. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4791; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4792. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4825. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4826. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4825; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4826. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4859. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4860. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4859; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4860. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4893. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4894. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4893; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4894. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4927. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4928. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4927; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4928. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4961. In one embodiment, the CD4 antibody comprises: a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4962. In one embodiment, the CD4 antibody comprises: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4961; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4962. In some embodiments, the CD4 antibody is a multispecific antibody. In some embodiments, the CD4 antibody is a bispecific antibody. In some embodiments, the CD4 antibody is a trispecific antibody. In some embodiments, the CD4 antibody is a quadraspecific antibody. In certain embodiments, the CD4 antibody is a multispecific antibody, wherein the second target is CD8. In certain embodiments, the CD8×CD4 multispecific antibody comprises a CD8 antibody provided herein and a CD4 antibody provided here.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2177, 2178, and 2179, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2180, 2181, and 2182, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2183, 2184, and 2185, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2186, 2187, and 2188, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2189, 2190, and 2191, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2192, 2193, and 2194, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2195, 2196, and 2197, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2198, 2199, and 2200, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2201, 2202, and 2203, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2204, 2205, and 2206, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2207; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2208. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2207. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:2208. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2207, and a VL having an amino acid sequence of SEQ ID NO:2208. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2207. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2208. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2207, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2208.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2211, 2212, and 2213, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2214, 2215, and 2216, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2217, 2218, and 2219, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2220, 2221, and 2222, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2223, 2224, and 2225, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2226, 2227, and 2228, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2229, 2230, and 2231, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2232, 2233, and 2234, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2235, 2236, and 2237, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2238, 2239, and 2240, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2241; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2242. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2241. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:2242. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2241, and a VL having an amino acid sequence of SEQ ID NO:2242. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2241. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2242. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2241, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2242.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2245, 2246, and 2247, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2248, 2249, and 2250, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2251, 2252, and 2253, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2254, 2255, and 2256, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2257, 2258, and 2259, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2260, 2261, and 2262, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2263, 2264, and 2265, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2266, 2267, and 2268, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2269, 2270, and 2271, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2272, 2273, and 2274, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2275; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2276. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2275. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:2276. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2275. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2276. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2275, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2276.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2279, 2280, and 2281, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2282, 2283, and 2284, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2285, 2286, and 2287, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2288, 2289, and 2290, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2291, 2292, and 2293, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2294, 2295, and 2296, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2297, 2298, and 2299, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2300, 2301, and 2302, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2303, 2304, and 2305, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2306, 2307, and 2308, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2309; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2310. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2309. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:2310. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2309, and a VL having an amino acid sequence of SEQ ID NO:2310. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence of SEQ ID NO:2311. In one aspect, provided herein is an antibody that binds CD4, comprising a light chain having an amino acid sequence of SEQ ID NO:2312. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence of SEQ ID NO:2311, and a light chain having an amino acid sequence of SEQ ID NO:2312. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2309. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2310. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2309, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2310. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2311. In one aspect, provided herein is an antibody that binds CD4, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2312. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2311, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2312.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2313, 2314, and 2315, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2316, 2317, and 2318, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2319, 2320, and 2321, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2322, 2323, and 2324, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2325, 2326, and 2327, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2328, 2329, and 2330, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2331, 2332, and 2333, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2334, 2335, and 2336, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2337, 2338, and 2339, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2340, 2341, and 2342, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2343; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2344. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2343. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:2344. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2343, and a VL having an amino acid sequence of SEQ ID NO:2344. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2343. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2344. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2343, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2344.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2347, 2348, and 2349, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2350, 2351, and 2352, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2353, 2354, and 2355, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2356, 2357, and 2358, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2359, 2360, and 2361, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2362, 2363, and 2364, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2365, 2366, and 2367, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2368, 2369, and 2370, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2371, 2372, and 2373, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2374, 2375, and 2376, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2377; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2378. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2377. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:2378. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2377, and a VL having an amino acid sequence of SEQ ID NO:2378. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2377. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2378. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2377, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2378.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2381, 2382, and 2383, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2384, 2385, and 2386, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2387, 2388, and 2389, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2390, 2391, and 2392, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2393, 2394, and 2395, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2396, 2397, and 2398, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2399, 2400, and 2401, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2402, 2403, and 2404, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2405, 2406, and 2407, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2408, 2409, and 2410, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2411; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2412. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2411. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:2412. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2411, and a VL having an amino acid sequence of SEQ ID NO:2412. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2411. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2412. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2411, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2412.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2415, 2416, and 2417, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2418, 2419, and 2420, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2421, 2422, and 2423, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2424, 2425, and 2426, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2427, 2428, and 2429, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2430, 2431, and 2432, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2433, 2434, and 2435, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2436, 2437, and 2438, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2439, 2440, and 2441, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2442, 2443, and 2444, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2445; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2446. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2445. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:2446. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2445, and a VL having an amino acid sequence of SEQ ID NO:2446. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence of SEQ ID NO:2447. In one aspect, provided herein is an antibody that binds CD4, comprising a light chain having an amino acid sequence of SEQ ID NO:2448. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence of SEQ ID NO:2447, and a light chain having an amino acid sequence of SEQ ID NO:2448. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2445. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2446. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2445, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2446. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2447. In one aspect, provided herein is an antibody that binds CD4, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2448. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2447, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2448.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2449, 2450, and 2451, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2452, 2453, and 2454, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2455, 2456, and 2457, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2458, 2459, and 2460, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2461, 2462, and 2463, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2464, 2465, and 2466, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2467, 2468, and 2469, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2470, 2471, and 2472, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2473, 2474, and 2475, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2476, 2477, and 2478, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2479; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2480. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2479. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:2480. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2479, and a VL having an amino acid sequence of SEQ ID NO:2480. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2479. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2480. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2479, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2480.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2483, 2484, and 2485, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2486, 2487, and 2488, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2489, 2490, and 2491, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2492, 2493, and 2494, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2495, 2496, and 2497, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2498, 2499, and 2500, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2501, 2502, and 2503, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2504, 2505, and 2506, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2507, 2508, and 2509, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2510, 2511, and 2512, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2513; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2514. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2513. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:2514. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2513, and a VL having an amino acid sequence of SEQ ID NO:2514. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence of SEQ ID NO:2515. In one aspect, provided herein is an antibody that binds CD4, comprising a light chain having an amino acid sequence of SEQ ID NO:2516. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence of SEQ ID NO:2515, and a light chain having an amino acid sequence of SEQ ID NO:2516. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2513. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2514. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2513, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2514. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2515. In one aspect, provided herein is an antibody that binds CD4, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2516. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2515, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2516.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2517, 2518, and 2519, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2520, 2521, and 2522, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2523, 2524, and 2525, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2526, 2527, and 2528, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2529, 2530, and 2531, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2532, 2533, and 2534, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2535, 2536, and 2537, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2538, 2539, and 2540, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2541, 2542, and 2543, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2544, 2545, and 2546, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2547; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2548. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2547. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:2548. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2547, and a VL having an amino acid sequence of SEQ ID NO:2548. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2547. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2548. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2547, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2548.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2551, 2552, and 2553, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2554, 2555, and 2556, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2557, 2558, and 2559, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2560, 2561, and 2562, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2563, 2564, and 2565, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2566, 2567, and 2568, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2569, 2570, and 2571, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2572, 2573, and 2574, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2575, 2576, and 2577, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2578, 2579, and 2580, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2581; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2582. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2581. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:2582. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2581, and a VL having an amino acid sequence of SEQ ID NO:2582. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2581. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2582. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2581, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2582.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2585, 2586, and 2587, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2588, 2589, and 2590, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2591, 2592, and 2593, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2594, 2595, and 2596, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2597, 2598, and 2599, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2600, 2601, and 2602, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2603, 2604, and 2605, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2606, 2607, and 2608, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2609, 2610, and 2611, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2612, 2613, and 2614, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2615; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2616. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2615. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:2616. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2615, and a VL having an amino acid sequence of SEQ ID NO:2616. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2615. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2616. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2615, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2616.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2619, 2620, and 2621, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2622, 2623, and 2624, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2625, 2626, and 2627, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2628, 2629, and 2630, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2631, 2632, and 2633, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2634, 2635, and 2636, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2637, 2638, and 2639, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2640, 2641, and 2642, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2643, 2644, and 2645, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2646, 2647, and 2648, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2649; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2650. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2649. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:2650. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2649, and a VL having an amino acid sequence of SEQ ID NO:2650. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2649. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2650. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2649, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2650.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2653, 2654, and 2655, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2656, 2657, and 2658, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2659, 2660, and 2661, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2662, 2663, and 2664, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2665, 2666, and 2667, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2668, 2669, and 2670, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2671, 2672, and 2673, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2674, 2675, and 2676, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2677, 2678, and 2679, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2680, 2681, and 2682, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2683; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2684. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2683. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:2684. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2683, and a VL having an amino acid sequence of SEQ ID NO:2684. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2683. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2684. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2683, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2684.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2687, 2688, and 2689, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2690, 2691, and 2692, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2693, 2694, and 2695, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2696, 2697, and 2698, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2699, 2700, and 2701, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2702, 2703, and 2704, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2705, 2706, and 2707, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2708, 2709, and 2710, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2711, 2712, and 2713, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2714, 2715, and 2716, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2717; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2718. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2717. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:2718. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2717, and a VL having an amino acid sequence of SEQ ID NO:2718. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2717. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2718. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2717, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2718.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2721, 2722, and 2723, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2724, 2725, and 2726, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2727, 2728, and 2729, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2730, 2731, and 2732, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2733, 2734, and 2735, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2736, 2737, and 2738, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2739, 2740, and 2741, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2742, 2743, and 2744, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2745, 2746, and 2747, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2748, 2749, and 2750, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2751; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2752. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2751. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:2752. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2751, and a VL having an amino acid sequence of SEQ ID NO:2752. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2751. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2752. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2751, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2752.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2755, 2756, and 2757, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2758, 2759, and 2760, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2761, 2762, and 2763, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2764, 2765, and 2766, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2767, 2768, and 2769, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2770, 2771, and 2772, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2773, 2774, and 2775, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2776, 2777, and 2778, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2779, 2780, and 2781, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2782, 2783, and 2784, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2785; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2786. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2785. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:2786. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2785, and a VL having an amino acid sequence of SEQ ID NO:2786. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2785. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2786. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2785, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2786.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2789, 2790, and 2791, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2792, 2793, and 2794, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2795, 2796, and 2797, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2798, 2799, and 2800, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2801, 2802, and 2803, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2804, 2805, and 2806, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2807, 2808, and 2809, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2810, 2811, and 2812, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2813, 2814, and 2815, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2816, 2817, and 2818, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2819; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2820. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2819. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:2820. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2819, and a VL having an amino acid sequence of SEQ ID NO:2820. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2819. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2820. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2819, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2820.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2823, 2824, and 2825, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2826, 2827, and 2828, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2829, 2830, and 2831, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2832, 2833, and 2834, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2835, 2836, and 2837, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2838, 2839, and 2840, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2841, 2842, and 2843, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2844, 2845, and 2846, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2847, 2848, and 2849, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2850, 2851, and 2852, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2853; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2854. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2853. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:2854. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2853, and a VL having an amino acid sequence of SEQ ID NO:2854. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2853. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2854. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2853, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2854.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2857, 2858, and 2859, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2860, 2861, and 2862, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2863, 2864, and 2865, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2866, 2867, and 2868, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2869, 2870, and 2871, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2872, 2873, and 2874, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2875, 2876, and 2877, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2878, 2879, and 2880, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2881, 2882, and 2883, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2884, 2885, and 2886, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2887; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2888. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2887. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:2888. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2887, and a VL having an amino acid sequence of SEQ ID NO:2888. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2887. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2888. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2887, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2888.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2891, 2892, and 2893, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2894, 2895, and 2896, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2897, 2898, and 2899, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2900, 2901, and 2902, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2903, 2904, and 2905, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2906, 2907, and 2908, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2909, 2910, and 2911, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2912, 2913, and 2914, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2915, 2916, and 2917, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2918, 2919, and 2920, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2921; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2922. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2921. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:2922. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2921, and a VL having an amino acid sequence of SEQ ID NO:2922. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2921. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2922. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2921, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2922.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2925, 2926, and 2927, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2928, 2929, and 2930, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2931, 2932, and 2933, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2934, 2935, and 2936, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2937, 2938, and 2939, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2940, 2941, and 2942, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2943, 2944, and 2945, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2946, 2947, and 2948, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2949, 2950, and 2951, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2952, 2953, and 2954, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2955; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2956. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2955. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:2956. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2955, and a VL having an amino acid sequence of SEQ ID NO:2956. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2955. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2956. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2955, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2956.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2959, 2960, and 2961, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2962, 2963, and 2964, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2965, 2966, and 2967, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2968, 2969, and 2970, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2971, 2972, and 2973, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2974, 2975, and 2976, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2977, 2978, and 2979, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2980, 2981, and 2982, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2983, 2984, and 2985, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2986, 2987, and 2988, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2989; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2990. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2989. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:2990. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:2989, and a VL having an amino acid sequence of SEQ ID NO:2990. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence of SEQ ID NO:2991. In one aspect, provided herein is an antibody that binds CD4, comprising a light chain having an amino acid sequence of SEQ ID NO:2992. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence of SEQ ID NO:2991, and a light chain having an amino acid sequence of SEQ ID NO:2992. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2989. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2990. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2989, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2990. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2991. In one aspect, provided herein is an antibody that binds CD4, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2992. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2991, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:2992.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2993, 2994, and 2995, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:2996, 2997, and 2998, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:2999, 3000, and 3001, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3002, 3003, and 3004, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3005, 3006, and 3007, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3008, 3009, and 3010, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3011, 3012, and 3013, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3014, 3015, and 3016, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3017, 3018, and 3019, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3020, 3021, and 3022, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3023; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3024. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3023. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:3024. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3023, and a VL having an amino acid sequence of SEQ ID NO:3024. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence of SEQ ID NO:3025. In one aspect, provided herein is an antibody that binds CD4, comprising a light chain having an amino acid sequence of SEQ ID NO:3026. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence of SEQ ID NO:3025, and a light chain having an amino acid sequence of SEQ ID NO:3026. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3023. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3024. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3023, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3024. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3025. In one aspect, provided herein is an antibody that binds CD4, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3026. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3025, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3026.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3027, 3028, and 3029, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3030, 3031, and 3032, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3033, 3034, and 3035, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3036, 3037, and 3038, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3039, 3040, and 3041, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3042, 3043, and 3044, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3045, 3046, and 3047, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3048, 3049, and 3050, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3051, 3052, and 3053, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3054, 3055, and 3056, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3057; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3058. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3057. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:3058. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3057, and a VL having an amino acid sequence of SEQ ID NO:3058. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3057. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3058. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3057, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3058.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3061, 3062, and 3063, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3064, 3065, and 3066, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3067, 3068, and 3069, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3070, 3071, and 3072, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3073, 3074, and 3075, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3076, 3077, and 3078, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3079, 3080, and 3081, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3082, 3083, and 3084, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3085, 3086, and 3087, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3088, 3089, and 3090, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3091; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3092. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3091. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:3092. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3091, and a VL having an amino acid sequence of SEQ ID NO:3092. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence of SEQ ID NO:3093. In one aspect, provided herein is an antibody that binds CD4, comprising a light chain having an amino acid sequence of SEQ ID NO:3094. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence of SEQ ID NO:3093, and a light chain having an amino acid sequence of SEQ ID NO:3094. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3091. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3092. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3091, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3092. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3093. In one aspect, provided herein is an antibody that binds CD4, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3094. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3093, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3094.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3095, 3096, and 3097, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3098, 3099, and 3100, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3101, 3102, and 3103, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3104, 3105, and 3106, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3107, 3108, and 3109, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3110, 3111, and 3112, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3113, 3114, and 3115, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3116, 3117, and 3118, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3119, 3120, and 3121, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3122, 3123, and 3124, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3125; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3126. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3125. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:3126. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3125, and a VL having an amino acid sequence of SEQ ID NO:3126. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3125. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3126. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3125, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3126.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3129, 3130, and 3131, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3132, 3133, and 3134, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3135, 3136, and 3137, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3138, 3139, and 3140, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3141, 3142, and 3143, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3144, 3145, and 3146, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3147, 3148, and 3149, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3150, 3151, and 3152, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3153, 3154, and 3155, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3156, 3157, and 3158, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3159; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3160. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3159. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:3160. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3159, and a VL having an amino acid sequence of SEQ ID NO:3160. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence of SEQ ID NO:3161. In one aspect, provided herein is an antibody that binds CD4, comprising a light chain having an amino acid sequence of SEQ ID NO:3162. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence of SEQ ID NO:3161, and a light chain having an amino acid sequence of SEQ ID NO:3162. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3159. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3160. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3159, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3160. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3161. In one aspect, provided herein is an antibody that binds CD4, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3162. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3161, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3162.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3163, 3164, and 3165, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3166, 3167, and 3168, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3169, 3170, and 3171, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3172, 3173, and 3174, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3175, 3176, and 3177, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3178, 3179, and 3180, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3181, 3182, and 3183, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3184, 3185, and 3186, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3187, 3188, and 3189, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3190, 3191, and 3192, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3193; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3194. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3193. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:3194. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3193, and a VL having an amino acid sequence of SEQ ID NO:3194. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3193. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3194. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3193, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3194.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3197, 3198, and 3199, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3200, 3201, and 3202, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3203, 3204, and 3205, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3206, 3207, and 3208, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3209, 3210, and 3211, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3212, 3213, and 3214, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3215, 3216, and 3217, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3218, 3219, and 3220, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3221, 3222, and 3223, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3224, 3225, and 3226, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3227; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3228. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3227. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:3228. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3227, and a VL having an amino acid sequence of SEQ ID NO:3228. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3227. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3228. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3227, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3228.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3231, 3232, and 3233, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3234, 3235, and 3236, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3237, 3238, and 3239, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3240, 3241, and 3242, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3243, 3244, and 3245, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3246, 3247, and 3248, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3249, 3250, and 3251, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3252, 3253, and 3254, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3255, 3256, and 3257, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3258, 3259, and 3260, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3261; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3262. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3261. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:3262. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3261, and a VL having an amino acid sequence of SEQ ID NO:3262. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3261. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3262. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3261, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3262.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3265, 3266, and 3267, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3268, 3269, and 3270, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3271, 3272, and 3273, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3274, 3275, and 3276, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3277, 3278, and 3279, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3280, 3281, and 3282, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3283, 3284, and 3285, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3286, 3287, and 3288, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3289, 3290, and 3291, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3292, 3293, and 3294, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3295; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3296. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3295. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:3296. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3295, and a VL having an amino acid sequence of SEQ ID NO:3296. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence of SEQ ID NO:3297. In one aspect, provided herein is an antibody that binds CD4, comprising a light chain having an amino acid sequence of SEQ ID NO:3298. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence of SEQ ID NO:3297, and a light chain having an amino acid sequence of SEQ ID NO:3298. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3295. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3296. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3295, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3296. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3297. In one aspect, provided herein is an antibody that binds CD4, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3298. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3297, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3298.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3299, 3300, and 3301, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3302, 3303, and 3304, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3305, 3306, and 3307, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3308, 3309, and 3310, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3311, 3312, and 3313, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3314, 3315, and 3316, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3317, 3318, and 3319, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3320, 3321, and 3322, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3323, 3324, and 3325, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3326, 3327, and 3328, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3329; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3330. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3329. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:3330. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3329, and a VL having an amino acid sequence of SEQ ID NO:3330. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3329. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3330. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3329, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3330.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3333, 3334, and 3335, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3336, 3337, and 3338, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3339, 3340, and 3341, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3342, 3343, and 3344, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3345, 3346, and 3347, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3348, 3349, and 3350, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3351, 3352, and 3353, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3354, 3355, and 3356, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3357, 3358, and 3359, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3360, 3361, and 3362, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3363; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3364. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3363. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:3364. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3363, and a VL having an amino acid sequence of SEQ ID NO:3364. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3363. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3364. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3363, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3364.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3367, 3368, and 3369, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3370, 3371, and 3372, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3373, 3374, and 3375, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3376, 3377, and 3378, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3379, 3380, and 3381, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3382, 3383, and 3384, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3385, 3386, and 3387, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3388, 3389, and 3390, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3391, 3392, and 3393, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3394, 3395, and 3396, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3397; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3398. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3397. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:3398. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3397, and a VL having an amino acid sequence of SEQ ID NO:3398. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence of SEQ ID NO:3399. In one aspect, provided herein is an antibody that binds CD4, comprising a light chain having an amino acid sequence of SEQ ID NO:3400. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence of SEQ ID NO:3399, and a light chain having an amino acid sequence of SEQ ID NO:3400. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3397. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3398. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3397, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3398. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3399. In one aspect, provided herein is an antibody that binds CD4, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3400. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3399, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3400.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3401, 3402, and 3403, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3404, 3405, and 3406, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3407, 3408, and 3409, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3410, 3411, and 3412, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3413, 3414, and 3415, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3416, 3417, and 3418, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3419, 3420, and 3421, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3422, 3423, and 3424, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3425, 3426, and 3427, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3428, 3429, and 3430, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3431; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3432. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3431. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:3432. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3431, and a VL having an amino acid sequence of SEQ ID NO:3432. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3431. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3432. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3431, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3432.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3435, 3436, and 3437, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3438, 3439, and 3440, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3441, 3442, and 3443, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3444, 3445, and 3446, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3447, 3448, and 3449, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3450, 3451, and 3452, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3453, 3454, and 3455, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3456, 3457, and 3458, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3459, 3460, and 3461, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3462, 3463, and 3464, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3465; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3466. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3465. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:3466. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3465, and a VL having an amino acid sequence of SEQ ID NO:3466. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3465. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3466. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3465, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3466.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3469, 3470, and 3471, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3472, 3473, and 3474, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3475, 3476, and 3477, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3478, 3479, and 3480, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3481, 3482, and 3483, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3484, 3485, and 3486, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3487, 3488, and 3489, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3490, 3491, and 3492, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3493, 3494, and 3495, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3496, 3497, and 3498, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3499; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3500. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3499. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:3500. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3499, and a VL having an amino acid sequence of SEQ ID NO:3500. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3499. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3500. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3499, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3500.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3503, 3504, and 3505, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3506, 3507, and 3508, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3509, 3510, and 3511, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3512, 3513, and 3514, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3515, 3516, and 3517, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3518, 3519, and 3520, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3521, 3522, and 3523, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3524, 3525, and 3526, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3527, 3528, and 3529, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3530, 3531, and 3532, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3533; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3534. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3533. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:3534. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3533, and a VL having an amino acid sequence of SEQ ID NO:3534. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3533. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3534. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3533, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3534.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3537, 3538, and 3539, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3540, 3541, and 3542, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3543, 3544, and 3545, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3546, 3547, and 3548, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3549, 3550, and 3551, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3552, 3553, and 3554, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3555, 3556, and 3557, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3558, 3559, and 3560, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3561, 3562, and 3563, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3564, 3565, and 3566, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3567; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3568. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3567. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:3568. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3567, and a VL having an amino acid sequence of SEQ ID NO:3568. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3567. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3568. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3567, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3568.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3571, 3572, and 3573, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3574, 3575, and 3576, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3577, 3578, and 3579, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3580, 3581, and 3582, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3583, 3584, and 3585, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3586, 3587, and 3588, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3589, 3590, and 3591, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3592, 3593, and 3594, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3595, 3596, and 3597, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3598, 3599, and 3600, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3601; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3602. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3601. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:3602. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3601, and a VL having an amino acid sequence of SEQ ID NO:3602. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3601. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3602. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3601, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3602.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3605, 3606, and 3607, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3608, 3609, and 3610, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3611, 3612, and 3613, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3614, 3615, and 3616, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3617, 3618, and 3619, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3620, 3621, and 3622, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3623, 3624, and 3625, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3626, 3627, and 3628, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3629, 3630, and 3631, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3632, 3633, and 3634, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3635; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3636. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3635. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:3636. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3635, and a VL having an amino acid sequence of SEQ ID NO:3636. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3635. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3636. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3635, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3636.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3639, 3640, and 3641, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3642, 3643, and 3644, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3645, 3646, and 3647, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3648, 3649, and 3650, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3651, 3652, and 3653, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3654, 3655, and 3656, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3657, 3658, and 3659, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3660, 3661, and 3662, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3663, 3664, and 3665, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3666, 3667, and 3668, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3669; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3670. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3669. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:3670. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3669, and a VL having an amino acid sequence of SEQ ID NO:3670. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3669. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3670. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3669, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3670.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3673, 3674, and 3675, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3676, 3677, and 3678, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3679, 3680, and 3681, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3682, 3683, and 3684, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3685, 3686, and 3687, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3688, 3689, and 3690, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3691, 3692, and 3693, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3694, 3695, and 3696, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3697, 3698, and 3699, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3700, 3701, and 3702, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3703; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3704. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3703. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:3704. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3703, and a VL having an amino acid sequence of SEQ ID NO:3704. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3703. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3704. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3703, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3704.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3707, 3708, and 3709, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3710, 3711, and 3712, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3713, 3714, and 3715, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3716, 3717, and 3718, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3719, 3720, and 3721, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3722, 3723, and 3724, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3725, 3726, and 3727, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3728, 3729, and 3730, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3731, 3732, and 3733, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3734, 3735, and 3736, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3737; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3738. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3737. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:3738. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3737, and a VL having an amino acid sequence of SEQ ID NO:3738. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3737. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3738. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3737, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3738.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3741, 3742, and 3743, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3744, 3745, and 3746, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3747, 3748, and 3749, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3750, 3751, and 3752, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3753, 3754, and 3755, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3756, 3757, and 3758, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3759, 3760, and 3761, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3762, 3763, and 3764, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3765, 3766, and 3767, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3768, 3769, and 3770, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3771; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3772. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3771. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:3772. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3771, and a VL having an amino acid sequence of SEQ ID NO:3772. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3771. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3772. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3771, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3772.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3775, 3776, and 3777, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3778, 3779, and 3780, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3781, 3782, and 3783, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3784, 3785, and 3786, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3787, 3788, and 3789, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3790, 3791, and 3792, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3793, 3794, and 3795, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3796, 3797, and 3798, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3799, 3800, and 3801, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3802, 3803, and 3804, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3805; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3806. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3805. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:3806. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3805, and a VL having an amino acid sequence of SEQ ID NO:3806. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3805. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3806. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3805, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3806.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3809, 3810, and 3811, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3812, 3813, and 3814, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3815, 3816, and 3817, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3818, 3819, and 3820, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3821, 3822, and 3823, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3824, 3825, and 3826, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3827, 3828, and 3829, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3830, 3831, and 3832, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3833, 3834, and 3835, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3836, 3837, and 3838, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3839; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3840. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3839. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:3840. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3839, and a VL having an amino acid sequence of SEQ ID NO:3840. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3839. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3840. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3839, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3840.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3843, 3844, and 3845, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3846, 3847, and 3848, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3849, 3850, and 3851, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3852, 3853, and 3854, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3855, 3856, and 3857, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3858, 3859, and 3860, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3861, 3862, and 3863, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3864, 3865, and 3866, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3867, 3868, and 3869, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3870, 3871, and 3872, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3873; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3874. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3873. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:3874. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3873, and a VL having an amino acid sequence of SEQ ID NO:3874. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence of SEQ ID NO:3875. In one aspect, provided herein is an antibody that binds CD4, comprising a light chain having an amino acid sequence of SEQ ID NO:3876. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence of SEQ ID NO:3875, and a light chain having an amino acid sequence of SEQ ID NO:3876. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3873. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3874. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3873, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3874. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3875. In one aspect, provided herein is an antibody that binds CD4, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3876. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3875, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3876.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3877, 3878, and 3879, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3880, 3881, and 3882, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3883, 3884, and 3885, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3886, 3887, and 3888, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3889, 3890, and 3891, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3892, 3893, and 3894, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3895, 3896, and 3897, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3898, 3899, and 3900, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3901, 3902, and 3903, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3904, 3905, and 3906, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3907; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3908. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3907. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:3908. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3907, and a VL having an amino acid sequence of SEQ ID NO:3908. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3907. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3908. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3907, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3908.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3911, 3912, and 3913, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3914, 3915, and 3916, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3917, 3918, and 3919, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3920, 3921, and 3922, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3923, 3924, and 3925, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3926, 3927, and 3928, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3929, 3930, and 3931, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3932, 3933, and 3934, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3935, 3936, and 3937, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3938, 3939, and 3940, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3941; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3942. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3941. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:3942. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3941, and a VL having an amino acid sequence of SEQ ID NO:3942. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3941. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3942. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3941, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3942.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3945, 3946, and 3947, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3948, 3949, and 3950, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3951, 3952, and 3953, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3954, 3955, and 3956, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3957, 3958, and 3959, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3960, 3961, and 3962, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3963, 3964, and 3965, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3966, 3967, and 3968, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3969, 3970, and 3971, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3972, 3973, and 3974, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3975; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3976. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3975. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:3976. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:3975, and a VL having an amino acid sequence of SEQ ID NO:3976. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence of SEQ ID NO:3977. In one aspect, provided herein is an antibody that binds CD4, comprising a light chain having an amino acid sequence of SEQ ID NO:3978. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence of SEQ ID NO:3977, and a light chain having an amino acid sequence of SEQ ID NO:3978. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3975. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3976. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3975, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3976. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3977. In one aspect, provided herein is an antibody that binds CD4, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3978. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3977, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:3978.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3979, 3980, and 3981, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3982, 3983, and 3984, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3985, 3986, and 3987, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3988, 3989, and 3990, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3991, 3992, and 3993, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:3994, 3995, and 3996, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:3997, 3998, and 3999, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4000, 4001, and 4002, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4003, 4004, and 4005, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4006, 4007, and 4008, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4009; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4010. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4009. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:4010. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4009, and a VL having an amino acid sequence of SEQ ID NO:4010. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4009. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4010. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4009, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4010.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4013, 4014, and 4015, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4016, 4017, and 4018, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4019, 4020, and 4021, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4022, 4023, and 4024, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4025, 4026, and 4027, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4028, 4029, and 4030, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4031, 4032, and 4033, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4034, 4035, and 4036, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4037, 4038, and 4039, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4040, 4041, and 4042, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4043; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4044. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4043. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:4044. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4043, and a VL having an amino acid sequence of SEQ ID NO:4044. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4043. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4044. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4043, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4044.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4047, 4048, and 4049, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4050, 4051, and 4052, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4053, 4054, and 4055, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4056, 4057, and 4058, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4059, 4060, and 4061, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4062, 4063, and 4064, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4065, 4066, and 4067, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4068, 4069, and 4070, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4071, 4072, and 4073, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4074, 4075, and 4076, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4077; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4078. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4077. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:4078. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4077, and a VL having an amino acid sequence of SEQ ID NO:4078. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4077. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4078. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4077, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4078.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4081, 4082, and 4083, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4084, 4085, and 4086, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4087, 4088, and 4089, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4090, 4091, and 4092, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4093, 4094, and 4095, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4096, 4097, and 4098, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4099, 4100, and 4101, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4102, 4103, and 4104, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4105, 4106, and 4107, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4108, 4109, and 4110, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4111; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4112. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4111. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:4112. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4111, and a VL having an amino acid sequence of SEQ ID NO:4112. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4111. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4112. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4111, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4112.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4115, 4116, and 4117, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4118, 4119, and 4120, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4121, 4122, and 4123, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4124, 4125, and 4126, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4127, 4128, and 4129, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4130, 4131, and 4132, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4133, 4134, and 4135, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4136, 4137, and 4138, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4139, 4140, and 4141, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4142, 4143, and 4144, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4145; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4146. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4145. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:4146. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4145, and a VL having an amino acid sequence of SEQ ID NO:4146. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4145. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4146. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4145, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4146.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4149, 4150, and 4151, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4152, 4153, and 4154, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4155, 4156, and 4157, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4158, 4159, and 4160, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4161, 4162, and 4163, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4164, 4165, and 4166, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4167, 4168, and 4169, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4170, 4171, and 4172, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4173, 4174, and 4175, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4176, 4177, and 4178, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4179; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4180. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4179. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:4180. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4179, and a VL having an amino acid sequence of SEQ ID NO:4180. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence of SEQ ID NO:4181. In one aspect, provided herein is an antibody that binds CD4, comprising a light chain having an amino acid sequence of SEQ ID NO:4182. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence of SEQ ID NO:4181, and a light chain having an amino acid sequence of SEQ ID NO:4182. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4179. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4180. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4179, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4180. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4181. In one aspect, provided herein is an antibody that binds CD4, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4182. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4181, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4182.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4183, 4184, and 4185, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4186, 4187, and 4188, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4189, 4190, and 4191, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4192, 4193, and 4194, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4195, 4196, and 4197, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4198, 4199, and 4200, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4201, 4202, and 4203, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4204, 4205, and 4206, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4207, 4208, and 4209, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4210, 4211, and 4212, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4213; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4214. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4213. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:4214. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4213, and a VL having an amino acid sequence of SEQ ID NO:4214. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence of SEQ ID NO:4215. In one aspect, provided herein is an antibody that binds CD4, comprising a light chain having an amino acid sequence of SEQ ID NO:4216. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence of SEQ ID NO:4215, and a light chain having an amino acid sequence of SEQ ID NO:4216. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4213. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4214. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4213, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4214. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4215. In one aspect, provided herein is an antibody that binds CD4, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4216. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4215, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4216.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4217, 4218, and 4219, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4220, 4221, and 4222, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4223, 4224, and 4225, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4226, 4227, and 4228, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4229, 4230, and 4231, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4232, 4233, and 4234, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4235, 4236, and 4237, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4238, 4239, and 4240, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4241, 4242, and 4243, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4244, 4245, and 4246, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4247; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4248. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4247. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:4248. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4247, and a VL having an amino acid sequence of SEQ ID NO:4248. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4247. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4248. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4247, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4248.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4251, 4252, and 4253, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4254, 4255, and 4256, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4257, 4258, and 4259, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4260, 4261, and 4262, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4263, 4264, and 4265, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4266, 4267, and 4268, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4269, 4270, and 4271, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4272, 4273, and 4274, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4275, 4276, and 4277, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4278, 4279, and 4280, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4281; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4282. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4281. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:4282. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4281, and a VL having an amino acid sequence of SEQ ID NO:4282. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence of SEQ ID NO:4283. In one aspect, provided herein is an antibody that binds CD4, comprising a light chain having an amino acid sequence of SEQ ID NO:4284. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence of SEQ ID NO:4283, and a light chain having an amino acid sequence of SEQ ID NO:4284. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4281. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4282. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4281, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4282. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4283. In one aspect, provided herein is an antibody that binds CD4, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4284. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4283, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4284.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4285, 4286, and 4287, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4288, 4289, and 4290, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4291, 4292, and 4293, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4294, 4295, and 4296, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4297, 4298, and 4299, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4300, 4301, and 4302, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4303, 4304, and 4305, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4306, 4307, and 4308, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4309, 4310, and 4311, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4312, 4313, and 4314, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4315; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4316. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4315. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:4316. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4315, and a VL having an amino acid sequence of SEQ ID NO:4316. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence of SEQ ID NO:4317. In one aspect, provided herein is an antibody that binds CD4, comprising a light chain having an amino acid sequence of SEQ ID NO:4318. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence of SEQ ID NO:4317, and a light chain having an amino acid sequence of SEQ ID NO:4318. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4315. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4316. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4315, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4316. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4317. In one aspect, provided herein is an antibody that binds CD4, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4318. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4317, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4318.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4319, 4320, and 4321, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4322, 4323, and 4324, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4325, 4326, and 4327, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4328, 4329, and 4330, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4331, 4332, and 4333, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4334, 4335, and 4336, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4337, 4338, and 4339, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4340, 4341, and 4342, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4343, 4344, and 4345, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4346, 4347, and 4348, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4349; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4350. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4349. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:4350. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4349, and a VL having an amino acid sequence of SEQ ID NO:4350. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4349. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4350. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4349, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4350.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4353, 4354, and 4355, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4356, 4357, and 4358, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4359, 4360, and 4361, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4362, 4363, and 4364, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4365, 4366, and 4367, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4368, 4369, and 4370, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4371, 4372, and 4373, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4374, 4375, and 4376, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4377, 4378, and 4379, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4380, 4381, and 4382, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4383; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4384. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4383. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:4384. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4383, and a VL having an amino acid sequence of SEQ ID NO:4384. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4383. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4384. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4383, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4384.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4387, 4388, and 4389, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4390, 4391, and 4392, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4393, 4394, and 4395, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4396, 4397, and 4398, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4399, 4400, and 4401, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4402, 4403, and 4404, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4405, 4406, and 4407, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4408, 4409, and 4410, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4411, 4412, and 4413, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4414, 4415, and 4416, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4417; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4418. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4417. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:4418. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4417, and a VL having an amino acid sequence of SEQ ID NO:4418. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4417. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4418. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4417, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4418.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4421, 4422, and 4423, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4424, 4425, and 4426, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4427, 4428, and 4429, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4430, 4431, and 4432, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4433, 4434, and 4435, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4436, 4437, and 4438, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4439, 4440, and 4441, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4442, 4443, and 4444, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4445, 4446, and 4447, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4448, 4449, and 4450, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4451; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4452. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4451. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:4452. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4451, and a VL having an amino acid sequence of SEQ ID NO:4452. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4451. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4452. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4451, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4452.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4455, 4456, and 4457, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4458, 4459, and 4460, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4461, 4462, and 4463, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4464, 4465, and 4466, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4467, 4468, and 4469, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4470, 4471, and 4472, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4473, 4474, and 4475, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4476, 4477, and 4478, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4479, 4480, and 4481, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4482, 4483, and 4484, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4485; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4486. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4485. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:4486. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4485, and a VL having an amino acid sequence of SEQ ID NO:4486. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4485. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4486. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4485, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4486.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4489, 4490, and 4491, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4492, 4493, and 4494, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4495, 4496, and 4497, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4498, 4499, and 4500, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4501, 4502, and 4503, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4504, 4505, and 4506, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4507, 4508, and 4509, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4510, 4511, and 4512, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4513, 4514, and 4515, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4516, 4517, and 4518, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4519; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4520. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4519. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:4520. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4519, and a VL having an amino acid sequence of SEQ ID NO:4520. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4519. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4520. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4519, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4520.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4523, 4524, and 4525, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4526, 4527, and 4528, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4529, 4530, and 4531, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4532, 4533, and 4534, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4535, 4536, and 4537, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4538, 4539, and 4540, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4541, 4542, and 4543, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4544, 4545, and 4546, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4547, 4548, and 4549, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4550, 4551, and 4552, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4553; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4554. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4553. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:4554. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4553, and a VL having an amino acid sequence of SEQ ID NO:4554. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4553. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4554. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4553, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4554.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4557, 4558, and 4559, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4560, 4561, and 4562, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4563, 4564, and 4565, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4566, 4567, and 4568, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4569, 4570, and 4571, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4572, 4573, and 4574, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4575, 4576, and 4577, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4578, 4579, and 4580, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4581, 4582, and 4583, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4584, 4585, and 4586, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4587; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4588. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4587. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:4588. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4587, and a VL having an amino acid sequence of SEQ ID NO:4588. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence of SEQ ID NO:4589. In one aspect, provided herein is an antibody that binds CD4, comprising a light chain having an amino acid sequence of SEQ ID NO:4590. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence of SEQ ID NO:4589, and a light chain having an amino acid sequence of SEQ ID NO:4590. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4587. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4588. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4587, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4588. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4589. In one aspect, provided herein is an antibody that binds CD4, comprising a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4590. In one aspect, provided herein is an antibody that binds CD4, comprising a heavy chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4589, and a light chain having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4590.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4591, 4592, and 4593, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4594, 4595, and 4596, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4597, 4598, and 4599, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4600, 4601, and 4602, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4603, 4604, and 4605, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4606, 4607, and 4608, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4609, 4610, and 4611, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4612, 4613, and 4614, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4615, 4616, and 4617, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4618, 4619, and 4620, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4621; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4622. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4621. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:4622. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4621, and a VL having an amino acid sequence of SEQ ID NO:4622. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4621. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4622. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4621, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4622.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4625, 4626, and 4627, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4628, 4629, and 4630, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4631, 4632, and 4633, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4634, 4635, and 4636, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4637, 4638, and 4639, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4640, 4641, and 4642, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4643, 4644, and 4645, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4646, 4647, and 4648, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4649, 4650, and 4651, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4652, 4653, and 4654, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4655; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4656. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4655. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:4656. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4655, and a VL having an amino acid sequence of SEQ ID NO:4656. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4655. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4656. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4655, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4656.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4659, 4660, and 4661, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4662, 4663, and 4664, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4665, 4666, and 4667, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4668, 4669, and 4670, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4671, 4672, and 4673, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4674, 4675, and 4676, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4677, 4678, and 4679, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4680, 4681, and 4682, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4683, 4684, and 4685, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4686, 4687, and 4688, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4689; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4690. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4689. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:4690. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4689, and a VL having an amino acid sequence of SEQ ID NO:4690. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4689. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4690. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4689, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4690.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4693, 4694, and 4695, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4696, 4697, and 4698, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4699, 4700, and 4701, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4702, 4703, and 4704, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4705, 4706, and 4707, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4708, 4709, and 4710, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4711, 4712, and 4713, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4714, 4715, and 4716, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4717, 4718, and 4719, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4720, 4721, and 4722, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4723; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4724. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4723. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:4724. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4723, and a VL having an amino acid sequence of SEQ ID NO:4724. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4723. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4724. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4723, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4724.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4727, 4728, and 4729, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4730, 4731, and 4732, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4733, 4734, and 4735, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4736, 4737, and 4738, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4739, 4740, and 4741, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4742, 4743, and 4744, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4745, 4746, and 4747, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4748, 4749, and 4750, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4751, 4752, and 4753, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4754, 4755, and 4756, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4757; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4758. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4757. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:4758. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4757, and a VL having an amino acid sequence of SEQ ID NO:4758. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4757. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4758. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4757, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4758.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4761, 4762, and 4763, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4764, 4765, and 4766, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4767, 4768, and 4769, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4770, 4771, and 4772, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4773, 4774, and 4775, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4776, 4777, and 4778, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4779, 4780, and 4781, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4476, 4477, and 4784, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4785, 4786, and 4787, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4788, 4789, and 4790, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4791; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4792. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4791. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:4792. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4791, and a VL having an amino acid sequence of SEQ ID NO:4792. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4791. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4792. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4791, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4792.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4795, 4796, and 4797, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4798, 4799, and 4800, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4801, 4802, and 4803, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4804, 4805, and 4806, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4807, 4808, and 4809, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4810, 4811, and 4812, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4813, 4814, and 4815, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4816, 4817, and 4818, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4819, 4820, and 4821, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4822, 4823, and 4824, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4825; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4826. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4825. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:4826. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4825, and a VL having an amino acid sequence of SEQ ID NO:4826. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4825. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4826. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4825, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4826.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4829, 4830, and 4831, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4832, 4833, and 4834, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4835, 4836, and 4837, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4838, 4839, and 4840, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4841, 4842, and 4843, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4844, 4845, and 4846, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4847, 4848, and 4849, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4850, 4851, and 4852, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4853, 4854, and 4855, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4856, 4857, and 4858, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4859; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4860. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4859. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:4860. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4859, and a VL having an amino acid sequence of SEQ ID NO:4860. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4859. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4860. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4859, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4860.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4863, 4864, and 4865, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4866, 4867, and 4868, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4869, 4870, and 4871, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4872, 4873, and 4874, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4875, 4876, and 4877, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4878, 4879, and 4880, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4881, 4882, and 4883, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4884, 4885, and 4886, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4887, 4888, and 4889, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4890, 4891, and 4892, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4893; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4894. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4893. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:4894. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4893, and a VL having an amino acid sequence of SEQ ID NO:4894. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4893. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4894. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4893, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4894.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4897, 4898, and 4899, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4900, 4901, and 4902, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4903, 4904, and 4905, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4906, 4907, and 4908, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4909, 4910, and 4911, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4912, 4913, and 4914, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4915, 4916, and 4917, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4918, 4919, and 4920, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4921, 4922, and 4923, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4924, 4925, and 4926, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4927; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4928. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4927. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:4928. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4927, and a VL having an amino acid sequence of SEQ ID NO:4928. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4927. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4928. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4927, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4928.


In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4931, 4932, and 4933, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4934, 4935, and 4936, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4937, 4938, and 4939, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4940, 4941, and 4942, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4943, 4944, and 4945, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4946, 4947, and 4948, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4949, 4950, and 4951, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4952, 4953, and 4954, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs:4955, 4956, and 4957, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having an amino acid sequence of SEQ ID NOs:4958, 4959, and 4960, respectively. In one aspect, provided herein is an antibody that binds CD4, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4961; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4962. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4961. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence of SEQ ID NO:4962. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence of SEQ ID NO:4961, and a VL having an amino acid sequence of SEQ ID NO:4962. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4961. In one aspect, provided herein is an antibody that binds CD4, comprising a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4962. In one aspect, provided herein is an antibody that binds CD4, comprising a VH having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4961, and a VL having an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:4962.


In one aspect, provided herein is an antibody that binds CD4 comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:2201, wherein the sixth amino acid is D or S; a VH CDR2 having an amino acid sequence of SEQ ID NO:2202, wherein the first amino acid is I or T, the second amino acid is N or K, the third amino acid is E or Q, the fourth amino acid is D or E, the sixth amino acid is G, N or S, and the seventh amino acid is D or E; and a VH CDR3 having an amino acid sequence of SEQ ID NO:2203, wherein the first amino acid is A or V, the ninth amino acid is A or S, and the twelfth amino acid is H or Y. In one aspect, provided herein is an antibody that binds CD4 comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:2204, wherein the fourth amino acid is R or S; a VL CDR2 having an amino acid sequence of SEQ ID NO:2205, wherein the first amino acid is A or G, and the second amino acid is A or V; and a VL CDR3 having an amino acid sequence of SEQ ID NO:2206. In one aspect, provided herein is an antibody that binds CD4 comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:2201, wherein the sixth amino acid is D or S; a VH CDR2 having an amino acid sequence of SEQ ID NO:2202, wherein the first amino acid is I or T, the second amino acid is N or K, the third amino acid is E or Q, the fourth amino acid is D or E, the sixth amino acid is G, N or S, and the seventh amino acid is D or E; a VH CDR3 having an amino acid sequence of SEQ ID NO:2203, wherein the first amino acid is A or V, the ninth amino acid is A or S, and the twelfth amino acid is H or Y; a VL CDR1 having an amino acid sequence of SEQ ID NO:2204, wherein the fourth amino acid is R or S; a VL CDR2 having an amino acid sequence of SEQ ID NO:2205, wherein the first amino acid is A or G, and the second amino acid is A or V; and a VL CDR3 having an amino acid sequence of SEQ ID NO:2206.


In one aspect, provided herein is an antibody that binds CD4 comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:2235, wherein the first amino acid is G or N, the fifth amino acid is I or S, the sixth amino acid is D, N, S or T, and the seventh amino acid is F or Y; a VH CDR2 having an amino acid sequence of SEQ ID NO:2236, wherein the second amino acid is N or Y, and the third amino acid is S or T; and a VH CDR3 having an amino acid sequence of SEQ ID NO:2237, wherein the third amino acid is D or E, the fourth amino acid is L or R, the sixth amino acid is A, D, K, or R, the seventh amino acid is R or Y, the eighth amino acid is L, N, or Y, the ninth amino acid is F or Y, and the twelfth amino acid is L, M, or V. In one aspect, provided herein is an antibody that binds CD4 comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:2238, wherein the first amino acid is H or Q, the second amino acid is D or G, and the fourth amino acid is G. T or S; a VL CDR2 having an amino acid sequence of SEQ ID NO:2239, wherein the first amino acid is A, D, V or Y, and the second amino acid is A or T; and a VL CDR3 having an amino acid sequence of SEQ ID NO:2240, wherein the first amino acid is L or Q, the third amino acid is H or Y, the fourth amino acid is D or N, the fifth amino acid is H, N, or S, and the sixth amino acid is L or Y. In one aspect, provided herein is an antibody that binds CD4 comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:2235, wherein the first amino acid is G or N, the fifth amino acid is I or S, the sixth amino acid is D, N, S or T, and the seventh amino acid is F or Y; a VH CDR2 having an amino acid sequence of SEQ ID NO:2236, wherein the second amino acid is N or Y, and the third amino acid is S or T; a VH CDR3 having an amino acid sequence of SEQ ID NO:2237, wherein the third amino acid is D or E, the fourth amino acid is L or R, the sixth amino acid is A, D, K, or R, the seventh amino acid is R or Y, the eighth amino acid is L, N, or Y, the ninth amino acid is F or Y, and the twelfth amino acid is L, M, or V; a VL CDR1 having an amino acid sequence of SEQ ID NO:2238, wherein the first amino acid is H or Q, the second amino acid is D or G, and the fourth amino acid is G. T or S; a VL CDR2 having an amino acid sequence of SEQ ID NO:2239, wherein the first amino acid is A, D, V or Y, and the second amino acid is A or T; and a VL CDR3 having an amino acid sequence of SEQ ID NO:2240, wherein the first amino acid is L or Q, the third amino acid is H or Y, the fourth amino acid is D or N, the fifth amino acid is H, N, or S, and the sixth amino acid is L or Y.


In one aspect, provided herein is an antibody that binds CD4 comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:2303, wherein the fourth amino acid is F or L; a VH CDR2 having an amino acid sequence of SEQ ID NO:2304, wherein the third amino acid is H or Q, and the sixth amino acid is S or T; and a VH CDR3 having an amino acid sequence of SEQ ID NO:2305, wherein the first amino acid is A, T, or V, the third amino acid is E, L, or V, the fourth amino acid is I, L, or V, and the ninth amino acid is P or S. In one aspect, provided herein is an antibody that binds CD4 comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:2306, wherein the second amino acid is D or G, the fourth amino acid is A or S, and the fifth amino acid is D, N, or S; a VL CDR2 having an amino acid sequence of SEQ ID NO:2307, wherein the first amino acid is A or D; and a VL CDR3 having an amino acid sequence of SEQ ID NO:2308, wherein the ninth amino acid is S or T. In one aspect, provided herein is an antibody that binds CD4 comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:2303, wherein the fourth amino acid is F or L; a VH CDR2 having an amino acid sequence of SEQ ID NO:2304, wherein the third amino acid is H or Q, and the sixth amino acid is S or T; a VH CDR3 having an amino acid sequence of SEQ ID NO:2305, wherein the first amino acid is A, T, or V, the third amino acid is E, L, or V, the fourth amino acid is I, L, or V, and the ninth amino acid is P or S; a VL CDR1 having an amino acid sequence of SEQ ID NO:2306, wherein the second amino acid is D or G, the fourth amino acid is A or S, and the fifth amino acid is D, N, or S; a VL CDR2 having an amino acid sequence of SEQ ID NO:2307, wherein the first amino acid is A or D; and a VL CDR3 having an amino acid sequence of SEQ ID NO:2308, wherein the ninth amino acid is S or T.


In one aspect, provided herein is an antibody that binds CD4 comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:2337, wherein the fifth amino acid is N, R or S, and the sixth amino acid is N or S; a VH CDR2 having an amino acid sequence of SEQ ID NO:2338, wherein the fifth amino acid is D or G; and a VH CDR3 having an amino acid sequence of SEQ ID NO:2339, wherein the fourth amino acid is A, D, G or N, the fifth amino acid is D, F, L or Y, the sixth amino acid is D, S, F or Y, and the tenth amino acid is L or M. In one aspect, provided herein is an antibody that binds CD4 comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:2340, wherein the second amino acid is N or S, the third amino acid is F, I, L, T or V, the fourth amino acid is I, S, T or Y, and the fifth amino acid is I, N, or S; a VL CDR2 having an amino acid sequence of SEQ ID NO:2341; and a VL CDR3 having an amino acid sequence of SEQ ID NO:2342, wherein the first amino acid is H or Q, the third amino acid is F, H, S or Y, and the fifth amino acid is F, I, N, S or T. In one aspect, provided herein is an antibody that binds CD4 comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:2337, wherein the fifth amino acid is N, R or S, and the sixth amino acid is N or S; a VH CDR2 having an amino acid sequence of SEQ ID NO:2338, wherein the fifth amino acid is D or G; a VH CDR3 having an amino acid sequence of SEQ ID NO:2339, wherein the fourth amino acid is A, D, G or N, the fifth amino acid is D, F, L or Y, the sixth amino acid is D, S, F or Y, and the tenth amino acid is L or M; a VL CDR1 having an amino acid sequence of SEQ ID NO:2340, wherein the second amino acid is N or S, the third amino acid is F, I, L, T or V, the fourth amino acid is I, S, T or Y, and the fifth amino acid is I, N, or S; a VL CDR2 having an amino acid sequence of SEQ ID NO:2341; and a VL CDR3 having an amino acid sequence of SEQ ID NO:2342, wherein the first amino acid is H or Q, the third amino acid is F, H, S or Y, and the fifth amino acid is F, I, N, S or T.


In one aspect, provided herein is an antibody that binds CD4 comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:2745, wherein the second amino acid is D or G; a VH CDR2 having an amino acid sequence of SEQ ID NO:2746, wherein the sixth amino acid is N or S; and a VH CDR3 having an amino acid sequence of SEQ ID NO:2747. In one aspect, provided herein is an antibody that binds CD4 comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:2748, wherein the fourth amino acid is G or S, the fifth amino acid is S or T, and the sixth amino acid is S or T; a VL CDR2 having an amino acid sequence of SEQ ID NO:2749, wherein the third amino acid is F or S; and a VL CDR3 having an amino acid sequence of SEQ ID NO:2750, wherein the fifth amino acid is R or S. In one aspect, provided herein is an antibody that binds CD4 comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:2745, wherein the second amino acid is D or G; a VH CDR2 having an amino acid sequence of SEQ ID NO:2746, wherein the sixth amino acid is N or S; a VH CDR3 having an amino acid sequence of SEQ ID NO:2747; a VL CDR1 having an amino acid sequence of SEQ ID NO:2748, wherein the fourth amino acid is G or S, the fifth amino acid is S or T, and the sixth amino acid is S or T; a VL CDR2 having an amino acid sequence of SEQ ID NO:2749, wherein the third amino acid is F or S; and a VL CDR3 having an amino acid sequence of SEQ ID NO:2750, wherein the fifth amino acid is R or S.


In one aspect, provided herein is an antibody that binds CD4 comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:2949, wherein the second amino acid is G or V, the fourth amino acid is I or S, and the seventh amino acid is F or Y, wherein the second amino acid is G or V, the fourth amino acid is I or S, and the seventh amino acid is F or Y; a VH CDR2 having an amino acid sequence of SEQ ID NO:2950; and a VH CDR3 having an amino acid sequence of SEQ ID NO:2951, wherein the eleventh amino acid is A or N. In one aspect, provided herein is an antibody that binds CD4 comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:2952; a VL CDR2 having an amino acid sequence of SEQ ID NO:2953, wherein the second amino acid is A or T; and a VL CDR3 having an amino acid sequence of SEQ ID NO:2954, wherein the third amino acid is C or Y. In one aspect, provided herein is an antibody that binds CD4 comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:2949, wherein the second amino acid is G or V, the fourth amino acid is I or S, and the seventh amino acid is F or Y, wherein the second amino acid is G or V, the fourth amino acid is I or S, and the seventh amino acid is F or Y; a VH CDR2 having an amino acid sequence of SEQ ID NO:2950; a VH CDR3 having an amino acid sequence of SEQ ID NO:2951, wherein the eleventh amino acid is A or N; a VL CDR1 having an amino acid sequence of SEQ ID NO:2952; a VL CDR2 having an amino acid sequence of SEQ ID NO:2953, wherein the second amino acid is A or T; and a VL CDR3 having an amino acid sequence of SEQ ID NO:2954, wherein the third amino acid is C or Y.


In one aspect, provided herein is an antibody that binds CD4 comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:3187, wherein the first amino acid is N or G, and the sixth amino acid is R, S, or T; a VH CDR2 having an amino acid sequence of SEQ ID NO:3188, wherein the second amino acid is C or Y, the fifth amino acid is E or G, the sixth amino acid is N, R or S, and the seventh amino acid is P or T; a VH CDR3 having an amino acid sequence of SEQ ID NO:3189, wherein the third amino acid is D or E, the fourth amino acid is L or R, the sixth amino acid is D or R, the seventh amino acid is L, P or Y, and the eighth amino acid is N or Y. In one aspect, provided herein is an antibody that binds CD4 comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:3190, wherein the first amino acid is H or Q; a VL CDR2 having an amino acid sequence of SEQ ID NO:3191, wherein the first amino acid is D or Y; and a VL CDR3 having an amino acid sequence of SEQ ID NO:3192, wherein the fifth amino acid is N or T, and the eighth amino acid is I or L. In one aspect, provided herein is an antibody that binds CD4 comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:3187, wherein the first amino acid is N or G, and the sixth amino acid is R, S, or T; a VH CDR2 having an amino acid sequence of SEQ ID NO:3188, wherein the second amino acid is C or Y, the fifth amino acid is E or G, the sixth amino acid is N, R or S, and the seventh amino acid is P or T; a VH CDR3 having an amino acid sequence of SEQ ID NO:3189, wherein the third amino acid is D or E, the fourth amino acid is L or R, the sixth amino acid is D or R, the seventh amino acid is L, P or Y, and the eighth amino acid is N or Y; a VL CDR1 having an amino acid sequence of SEQ ID NO:3190, wherein the first amino acid is H or Q; a VL CDR2 having an amino acid sequence of SEQ ID NO:3191, wherein the first amino acid is D or Y; and a VL CDR3 having an amino acid sequence of SEQ ID NO:3192, wherein the fifth amino acid is N or T, and the eighth amino acid is I or L.


In one aspect, provided herein is an antibody that binds CD4 comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:3663, wherein the sixth amino acid is G, N, S or T, the seventh amino acid is F or Y, and the eighth amino acid is F or Y; a VH CDR2 having an amino acid sequence of SEQ ID NO:3664, wherein the second amino acid is C or Y, the third amino acid is A, I, S or T, the fourth amino acid is S or T, the fifth amino acid is E or G, and the sixth amino acid is N or S; and a VH CDR3 having an amino acid sequence of SEQ ID NO:3665, wherein the third amino acid is D or E, the fourth amino acid is L or R, the sixth amino acid is D, G, or R, the seventh amino acid is L, P, or Y, and the eighth amino acid is N or Y. In one aspect, provided herein is an antibody that binds CD4 comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:3666, wherein the fifth amino acid is K or N; a VL CDR2 having an amino acid sequence of SEQ ID NO:3667, wherein the first amino acid is A, D, G or N; and a VL CDR3 having an amino acid sequence of SEQ ID NO:3668, wherein the fifth amino acid is N or S, and the eighth amino acid is I or L. In one aspect, provided herein is an antibody that binds CD4 comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:3663, wherein the sixth amino acid is G, N, S or T, the seventh amino acid is F or Y, and the eighth amino acid is F or Y; a VH CDR2 having an amino acid sequence of SEQ ID NO:3664, wherein the second amino acid is C or Y, the third amino acid is A, I, S or T, the fourth amino acid is S or T, the fifth amino acid is E or G, and the sixth amino acid is N or S; a VH CDR3 having an amino acid sequence of SEQ ID NO:3665, wherein the third amino acid is D or E, the fourth amino acid is L or R, the sixth amino acid is D, G, or R, the seventh amino acid is L, P, or Y, and the eighth amino acid is N or Y; a VL CDR1 having an amino acid sequence of SEQ ID NO:3666, wherein the fifth amino acid is K or N; a VL CDR2 having an amino acid sequence of SEQ ID NO:3667, wherein the first amino acid is A, D, G or N; and a VL CDR3 having an amino acid sequence of SEQ ID NO:3668, wherein the fifth amino acid is N or S, and the eighth amino acid is I or L.


In one aspect, provided herein is an antibody that binds CD4 comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:3221, wherein the sixth amino acid is D or S; a VH CDR2 having an amino acid sequence of SEQ ID NO:3222, wherein the eighth amino acid is K or deleted; and a VH CDR3 having an amino acid sequence of SEQ ID NO:3223, wherein the ninth amino acid is A or S. In one aspect, provided herein is an antibody that binds CD4 comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:3224; a VL CDR2 having an amino acid sequence of SEQ ID NO:3225, wherein the second amino acid is A or V; and a VL CDR3 having an amino acid sequence of SEQ ID NO:3226, wherein the fifth amino acid is I or S. In one aspect, provided herein is an antibody that binds CD4 comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:3221, wherein the sixth amino acid is D or S; a VH CDR2 having an amino acid sequence of SEQ ID NO:3222, wherein the eighth amino acid is K or deleted; a VH CDR3 having an amino acid sequence of SEQ ID NO:3223, wherein the ninth amino acid is A or S; a VL CDR1 having an amino acid sequence of SEQ ID NO:3224; a VL CDR2 having an amino acid sequence of SEQ ID NO:3225, wherein the second amino acid is A or V; and a VL CDR3 having an amino acid sequence of SEQ ID NO:3226, wherein the fifth amino acid is I or S.


In one aspect, provided herein is an antibody that binds CD4 comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:3391, wherein the second amino acid is D or G, and the fifth amino acid is G, R or S; a VH CDR2 having an amino acid sequence of SEQ ID NO:3392, wherein the third amino acid is A or T, and the sixth amino acid is R or S; and a VH CDR3 having an amino acid sequence of SEQ ID NO:3393, wherein the second amino acid is R or T, the fourth amino acid is E or G, the sixth amino acid is P or V, the seventh amino acid is G or T, the ninth amino acid is A or S, the tenth amino acid is L or F, and the twelfth amino acid is I or Y. In one aspect, provided herein is an antibody that binds CD4 comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:3394; a VL CDR2 having an amino acid sequence of SEQ ID NO:3395; and a VL CDR3 having an amino acid sequence of SEQ ID NO:3396, wherein the third amino acid is H or R. In one aspect, provided herein is an antibody that binds CD4 comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:3391, wherein the second amino acid is D or G, and the fifth amino acid is G, R or S; a VH CDR2 having an amino acid sequence of SEQ ID NO:3392, wherein the third amino acid is A or T, and the sixth amino acid is R or S; a VH CDR3 having an amino acid sequence of SEQ ID NO:3393, wherein the second amino acid is R or T, the fourth amino acid is E or G, the sixth amino acid is P or V, the seventh amino acid is G or T, the ninth amino acid is A or S, the tenth amino acid is L or F, and the twelfth amino acid is I or Y; a VL CDR1 having an amino acid sequence of SEQ ID NO:3394; a VL CDR2 having an amino acid sequence of SEQ ID NO:3395; and a VL CDR3 having an amino acid sequence of SEQ ID NO:3396, wherein the third amino acid is H or R.


In one aspect, provided herein is an antibody that binds CD4 comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:3867, wherein the third amino acid is I or T; a VH CDR2 having an amino acid sequence of SEQ ID NO:3868, wherein the third amino acid is E or Q; and a VH CDR3 having an amino acid sequence of SEQ ID NO:3869, wherein the fourth amino acid is G or N, the seventh amino acid is S or Y, and the eighth amino acid is G or Y. In one aspect, provided herein is an antibody that binds CD4 comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:3870, wherein the fifth amino acid is N or D; a VL CDR2 having an amino acid sequence of SEQ ID NO:3871; and a VL CDR3 having an amino acid sequence of SEQ ID NO:3872, wherein the second amino acid is H or L, and the third amino acid is D or H. In one aspect, provided herein is an antibody that binds CD4 comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:3867, wherein the third amino acid is I or T; a VH CDR2 having an amino acid sequence of SEQ ID NO:3868, wherein the third amino acid is E or Q; a VH CDR3 having an amino acid sequence of SEQ ID NO:3869, wherein the fourth amino acid is G or N, the seventh amino acid is S or Y, and the eighth amino acid is G or Y; a VL CDR1 having an amino acid sequence of SEQ ID NO:3870, wherein the fifth amino acid is N or D; a VL CDR2 having an amino acid sequence of SEQ ID NO:3871; and a VL CDR3 having an amino acid sequence of SEQ ID NO:3872, wherein the second amino acid is H or L, and the third amino acid is D or H.


In one aspect, provided herein is an antibody that binds CD4 comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:4581; a VH CDR2 having an amino acid sequence of SEQ ID NO:4582, wherein the third amino acid is H or Q, and the sixth amino acid is N or S; and a VH CDR3 having an amino acid sequence of SEQ ID NO:4583, wherein the sixth amino acid is F, W or Y. In one aspect, provided herein is an antibody that binds CD4 comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:4584, wherein the first amino acid is P or Q, the second amino acid is D or G, the fourth amino acid is A or S, and the fifth amino acid is D or N; a VL CDR2 having an amino acid sequence of SEQ ID NO:4585; and a VL CDR3 having an amino acid sequence of SEQ ID NO:4586, wherein the eight amino acid is L or Y. In one aspect, provided herein is an antibody that binds CD4 comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:4581; a VH CDR2 having an amino acid sequence of SEQ ID NO:4582, wherein the third amino acid is H or Q, and the sixth amino acid is N or S; a VH CDR3 having an amino acid sequence of SEQ ID NO:4583, wherein the sixth amino acid is F, W or Y; a VL CDR1 having an amino acid sequence of SEQ ID NO:4584, wherein the first amino acid is P or Q, the second amino acid is D or G, the fourth amino acid is A or S, and the fifth amino acid is D or N; a VL CDR2 having an amino acid sequence of SEQ ID NO:4585; and a VL CDR3 having an amino acid sequence of SEQ ID NO:4586, wherein the eight amino acid is L or Y.


In another aspect, provided herein is an antibody that competes for binding to CD4 with any of the CD4 antibodies described herein. In another aspect, provided herein is an antibody that binds to the same epitope as any of the CD4 antibodies described herein. In another aspect, provided is a CD4 antibody that binds an epitope on CD4 that overlaps with the epitope on CD4 bound by a CD4 antibody described herein.


In one aspect, provided is an antibody that competes for binding to CD4 with a CD4 reference antibody. In another aspect, provided is a CD4 antibody that binds to the same CD4 epitope as a CD4 reference antibody. In another aspect, provided is a CD4 antibody that binds an epitope on CD4 that overlaps with the epitope on CD4 bound by a CD4 reference antibody. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2207; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2208. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2241; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2242. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2275; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2276. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2309; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2310. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2343; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2344. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2377; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2378. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2411; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2412. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2445; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2446. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2479; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2480. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2513; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2514. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2547; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2548. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2581; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2582. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2615; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2616. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2649; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2650. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2683; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2684. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2717; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2718. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2751; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2752. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2785; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2786. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2819; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2820. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2853; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2854. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2887; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2888. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2921; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2922. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2955; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2956. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2989; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2990. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3023; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3024. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3057; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3058. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3091; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3092. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3125; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3126. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3159; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3160. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3193; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3194. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3227; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3228. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3261; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3262. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3295; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3296. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3329; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3330. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3363; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3364. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3397; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3398. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3431; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3432. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3465; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3466. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3499; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3500. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3533; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3534. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3567; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3568. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3601; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3602. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3635; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3636. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3669; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3670. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3703; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3704. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3737; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3738. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3771; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3772. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3805; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3806. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3839; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3840. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3873; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3874. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3907; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3908. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3941; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3942. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3975; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3976. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4009; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4010. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4043; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4044. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4077; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4078. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4111; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4112. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4145; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4146. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4179; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4180. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4213; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4214. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4247; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4248. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4281; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4282. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4315; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4316. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4349; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4350. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4383; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4384. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4417; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4418. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4451; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4452. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4485; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4486. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4519; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4520. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4553; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4554. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4587; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4588. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4621; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4622. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4655; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4656. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4689; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4690. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4723; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4724. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4757; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4758. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4791; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4792. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4825; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4826. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4859; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4860. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4893; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4894. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4927; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4928. In one embodiment, the CD4 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4961; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4962.


In another aspect, provided herein is a multispecific antibody that binds CD4. In some embodiments, the multispecific antibody is a bispecific antibody. In some embodiments, the multispecific antibody is a trispecific antibody.


In some embodiments, the multispecific antibody is a quadraspecific antibody. In one embodiment, the multispecific CD4 antibody comprises: (a) a first binding domain that binds CD4, and (b) a second binding domain that binds to a second target. In one embodiment, the multispecific CD4 antibody comprises: (a) a first binding domain that binds CD4, and (b) a second binding domain that binds to a second target, and (c) a third binding domain that binds to a third target. In one embodiment, the multispecific CD4 antibody comprises: (a) a first binding domain that binds CD4, and (b) a second binding domain that binds to a second target, (c) a third binding domain that binds to a third target, and (d) a fourth binding domain that binds to a fourth target.


In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2207; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2208. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2241; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2242. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2275; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2276. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2309; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2310. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2343; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2344. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2377; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2378. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2411; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2412. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2445; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2446. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2479; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2480. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2513; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2514. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2547; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2548. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2581; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2582. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2615; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2616. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2649; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2650. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2683; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2684. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2717; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2718. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2751; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2752. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2785; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2786. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2819; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2820. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2853; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2854. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2887; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2888. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2921; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2922. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2955; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2956. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2989; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2990. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3023; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3024. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3057; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3058. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3091; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3092. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3125; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3126. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3159; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3160. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3193; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3194. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3227; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3228. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3261; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3262. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3295; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3296. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3329; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3330. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3363; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3364. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3397; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3398. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3431; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3432. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3465; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3466. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3499; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3500. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3533; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3534. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3567; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3568. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3601; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3602. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3635; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3636. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3669; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3670. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3703; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3704. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3737; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3738. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3771; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3772. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3805; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3806. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3839; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3840. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3873; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3874. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3907; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3908. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3941; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3942. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3975; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3976. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4009; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4010. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4043; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4044. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4077; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4078. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4111; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4112. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4145; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4146. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4179; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4180. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4213; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4214. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4247; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4248. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4281; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4282. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4315; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4316. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4349; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4350. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4383; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4384. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4417; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4418. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4451; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4452. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4485; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4486. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4519; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4520. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4553; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4554. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4587; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4588. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4621; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4622. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4655; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4656. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4689; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4690. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4723; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4724. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4757; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4758. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4791; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4792. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4825; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4826. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4859; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4860. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4893; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4894. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4927; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4928. In one embodiment, the first binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4961; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4962.


In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the first binding domain that binds CD4 are according to the Kabat numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the first binding domain that binds CD4 are according to the Chothia numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the first binding domain that binds CD4 are according to the AbM numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the first binding domain that binds CD4 are according to the Contact numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the first binding domain that binds CD4 are according to the IMGT numbering system.


In some embodiments, the first binding domain binds a CD4 antigen. In some embodiments, the first binding domain binds a CD4 epitope. In some embodiments, the first binding domain specifically binds to CD4. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the first binding domain form a binding site for an antigen of the CD4. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the first binding domain form a binding site for an epitope of the CD4. In some embodiments, the CD4 is present on the surface of a T cell.


In some embodiments of the multispecific CD4 antibodies provided herein, the second target is not a CD4 antigen. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is not a CD4 antigen. In some embodiments of the multispecific CD4 antibodies provided herein, the fourth target is not a CD4 antigen. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is not a CD4 antigen, and the third target is not a CD4 antigen. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is not a CD4 antigen, and the fourth target is not a CD4 antigen. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is not a CD4 antigen, and the fourth target is not a CD4 antigen. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is not a CD4 antigen, the third target is not a CD4 antigen, and the fourth target is not a CD4 antigen. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is not a CD4 epitope. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is not a CD4 epitope. In some embodiments of the multispecific CD4 antibodies provided herein, the fourth target is not a CD4 epitope. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is not a CD4 epitope, and the third target is not a CD4 epitope. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is not a CD4 epitope, and the fourth target is not a CD4 epitope. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is not a CD4 epitope, and the fourth target is not a CD4 epitope. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is not a CD4 epitope, the third target is not a CD4 epitope, and the fourth target is not a CD4 epitope.


In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is a T cell receptor (TCR) complex. As used herein, “TCR complex” refers to a known TCR complex comprising TCRα and TCRβ chains, CD3ε, CD3γ, CD3δ, and CD3ζ molecules. In certain embodiments, TCRα and TCRβ chains are replaced by TCRγ and TCRδ chains. The amino acid sequences of the various proteins forming the TCR complex are known. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD3. In some embodiments, CD3 comprises CD3ε. In some embodiments, CD3 comprises CD3γ. In some embodiments, CD3 comprises CD3δ. In some embodiments, CD3 comprises CD3ζ. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD3ε. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD3γ. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD3δ. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD3ζ. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is a TCRα chain. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is a TCRβ chain. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is a TCRγ chain. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is a TCRδ chain. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is a T cell costimulatory molecule. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD28. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CTLA4. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is ICOS. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is 4-1BB. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is GITR. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD27. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is OX40. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD40L. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is HVEM. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is Galectin-9. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is TIM-1. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is LFA1. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD2. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is PD1. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is a TCR complex. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is CD3. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is CD3ε. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is CD3γ. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is CD3δ. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is CD3ζ. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is a TCRα chain. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is a TCRβ chain. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is a TCRγ chain. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is a TCRδ chain. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is a T cell costimulatory molecule. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is CD28. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is CTLA4. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is ICOS. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is 4-1BB. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is GITR. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is CD27. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is OX40. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is CD40L. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is HVEM. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is Galectin-9. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is TIM-1. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is LFA1. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is CD2. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is PD1. In some embodiments of the multispecific CD4 antibodies provided herein, the fourth target is a TCR complex. In some embodiments of the multispecific CD4 antibodies provided herein, the fourth target is CD3. In some embodiments of the multispecific CD4 antibodies provided herein, the fourth target is CD3ε. In some embodiments of the multispecific CD4 antibodies provided herein, the fourth target is CD3γ. In some embodiments of the multispecific CD4 antibodies provided herein, the fourth target is CD3δ. In some embodiments of the multispecific CD4 antibodies provided herein, the fourth target is CD3ζ. In some embodiments of the multispecific CD4 antibodies provided herein, the fourth target is a TCRα chain. In some embodiments of the multispecific CD4 antibodies provided herein, the fourth target is a TCRβ chain. In some embodiments of the multispecific CD4 antibodies provided herein, the fourth target is a TCRγ chain. In some embodiments of the multispecific CD4 antibodies provided herein, the fourth target is a TCRδ chain. In some embodiments of the multispecific CD4 antibodies provided herein, the fourth target is a T cell costimulatory molecule. In some embodiments of the multispecific CD4 antibodies provided herein, the fourth target is CD28. In some embodiments of the multispecific CD4 antibodies provided herein, the fourth target is CTLA4. In some embodiments of the multispecific CD4 antibodies provided herein, the fourth target is ICOS. In some embodiments of the multispecific CD4 antibodies provided herein, the fourth target is 4-1BB. In some embodiments of the multispecific CD4 antibodies provided herein, the fourth target is GITR. In some embodiments of the multispecific CD4 antibodies provided herein, the fourth target is CD27. In some embodiments of the multispecific CD4 antibodies provided herein, the fourth target is OX40. In some embodiments of the multispecific CD4 antibodies provided herein, the fourth target is CD40L. In some embodiments of the multispecific CD4 antibodies provided herein, the fourth target is HVEM. In some embodiments of the multispecific CD4 antibodies provided herein, the fourth target is Galectin-9. In some embodiments of the multispecific CD4 antibodies provided herein, the fourth target is TIM-1. In some embodiments of the multispecific CD4 antibodies provided herein, the four target is LFA1. In some embodiments of the multispecific CD4 antibodies provided herein, the fourth target is CD2. In some embodiments of the multispecific CD4 antibodies provided herein, the fourth target is PD1. In some embodiments, the second target is CD8. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is CD3. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is TCRα chain. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is a TCRβ chain. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is a TCRγ chain. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is a TCRδ chain. In some embodiments of the multispecific CD4 antibodies provided herein, the third target is CD28. In some embodiments of the multispecific CD4 antibodies provided herein, the fourth target is CD28.


In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, and the third target is a TCR complex. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, and the third target is CD3. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, and the third target is CD3ε. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, and the third target is CD3γ. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, and the third target is CD3δ. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, and the third target is CD3ζ. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, and the third target is a TCRα chain. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, and the third target is a TCRβ chain. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, and the third target is a TCRγ chain.


In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, and the third target is a T cell costimulatory molecule. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, and the third target is CD28. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, and the third target is CTLA4. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, and the third target is ICOS. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, and the third target is 4-1BB. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, and the third target is GITR. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, and the third target is CD27. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, and the third target is OX40. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, and the third target is CD40L. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, and the third target is HVEM. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, and the third target is Galectin-9. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, and the third target is TIM-1. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, and the third target is LFA1. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, and the third target is CD2. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, and the third target is PD1.


In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, the third target is a TCR complex, and the fourth target is a T cell costimulatory molecule. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, the third target is CD3, and the fourth target is a T cell costimulatory molecule. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, the third target is CD3ε, and the fourth target is a T cell costimulatory molecule. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, the third target is CD3γ, and the fourth target is a T cell costimulatory molecule. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, the third target is CD3δ, and the fourth target is a T cell costimulatory molecule. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, the third target is CD3ζ, and the fourth target is a T cell costimulatory molecule. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, the third target is a TCRα chain, and the fourth target is a T cell costimulatory molecule. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, the third target is a TCRβ chain, and the fourth target is a T cell costimulatory molecule. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD8, the third target is a TCRγ chain, and the fourth target is a T cell costimulatory molecule. In certain embodiments, the T cell costimulatory molecule is CD28. In certain embodiments, the T cell costimulatory molecule is CTLA4. In certain embodiments, the T cell costimulatory molecule is ICOS. In certain embodiments, the T cell costimulatory molecule is 4-1BB. In certain embodiments, the T cell costimulatory molecule is GITR. In certain embodiments, the T cell costimulatory molecule is CD27. In certain embodiments, the T cell costimulatory molecule is OX40. In certain embodiments, the T cell costimulatory molecule is CD40L. In certain embodiments, the T cell costimulatory molecule is HVEM. In certain embodiments, the T cell costimulatory molecule is Galectin-9. In certain embodiments, the T cell costimulatory molecule is TIM-1. In certain embodiments, the T cell costimulatory molecule is LFA1. In certain embodiments, the T cell costimulatory molecule is CD2. In certain embodiments, the T cell costimulatory molecule is PD1.


In some embodiments of the multispecific CD4 antibodies provided herein, the second target is a TCR complex, and the third target is a T cell costimulatory molecule. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD3, and the third target is a T cell costimulatory molecule. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD3ε, and the third target is a T cell costimulatory molecule. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD3γ, and the third target is a T cell costimulatory molecule. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD3δ, and the third target is a T cell costimulatory molecule. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is CD3ζ, and the third target is a T cell costimulatory molecule. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is a TCRα chain, and the third target is a T cell costimulatory molecule. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is a TCRβ chain, and the third target is a T cell costimulatory molecule. In some embodiments of the multispecific CD4 antibodies provided herein, the second target is a TCRγ chain, and the third target is a T cell costimulatory molecule. In certain embodiments, the T cell costimulatory molecule is CD28. In certain embodiments, the T cell costimulatory molecule is CTLA4. In certain embodiments, the T cell costimulatory molecule is ICOS. In certain embodiments, the T cell costimulatory molecule is 4-1BB. In certain embodiments, the T cell costimulatory molecule is GITR. In certain embodiments, the T cell costimulatory molecule is CD27. In certain embodiments, the T cell costimulatory molecule is OX40. In certain embodiments, the T cell costimulatory molecule is CD40L. In certain embodiments, the T cell costimulatory molecule is HVEM. In certain embodiments, the T cell costimulatory molecule is Galectin-9. In certain embodiments, the T cell costimulatory molecule is TIM-1. In certain embodiments, the T cell costimulatory molecule is LFA1. In certain embodiments, the T cell costimulatory molecule is CD2. In certain embodiments, the T cell costimulatory molecule is PD1.


In a specific embodiment, the target is from a mammal. In a specific embodiment, the target is from a rat. In a specific embodiment, the target is from a mouse. In a specific embodiment, the target is from a primate. In a specific embodiment, the target is from a human.


In specific embodiments, provided is a multispecific antibody comprising a CD4 antibody provided herein in a knob-in-hole format. In specific embodiments, provided is a bispecific antibody comprising a CD4 antibody provided herein in a knob-in-hole format. In specific embodiments, provided is a trispecific antibody comprising a CD4 antibody provided herein in a knob-in-hole format. In specific embodiments, provided is a quadraspecific antibody comprising a CD4 antibody provided herein in a knob-in-hole format. Other specificities can be added to an antibody in knob-in-hole format using methods well known in the art (e.g., adding an scFv to the N-terminus or C-terminus). In addition, other formats and methods of making multispecific antibodies are also known in the art and contemplated. In some embodiments, a CD4 antibody provided herein is comprised in a bispecific antibody. In some embodiments, a CD4 antibody provided herein is comprised in a trispecific antibody. In some embodiments, a CD4 antibody provided herein is comprised in a quadraspecific antibody. In some embodiments, a CD4 bispecific antibody provided herein is comprised in a multispecific antibody.


In certain embodiments, a multispecific antibody provided herein comprises a first binding domain comprising a CD4 antibody provided herein that binds to a first CD4 epitope, and a second binding domain that binds to a second epitope, wherein the first CD4 epitope and the second epitope are not the same. In certain embodiments, a bispecific antibody provided herein comprises a first binding domain comprising a CD4 antibody provided herein that binds to a first CD4 epitope, and a second binding domain that binds to a second epitope, wherein the first CD4 epitope and the second epitope are not the same. In certain embodiments, a trispecific antibody provided herein comprises a first binding domain comprising a CD4 antibody provided herein that binds to a first CD4 epitope, a second binding domain that binds to a second epitope, and a third binding domain that binds to a third epitope, wherein the first CD4 epitope, the second epitope, and the third epitope are not the same. In certain embodiments, a quadraspecific antibody provided herein comprises a first binding domain comprising a CD4 antibody provided herein that binds to a first CD4 epitope, a second binding domain that binds to a second epitope, a third binding domain that binds to a third epitope, and a fourth binding domain that binds to a fourth epitope, wherein the first CD4 epitope, the second epitope, the third epitope, and the fourth epitope are not the same. In certain embodiments, a multispecific antibody provided herein comprises a first binding domain comprising a CD4 antibody provided herein that binds to a first CD4 antigen, and a second binding domain that binds to a second antigen, wherein the first CD4 antigen and the second antigen are not the same. In certain embodiments, a bispecific antibody provided herein comprises a first binding domain comprising a CD4 antibody provided herein that binds to a first CD4 antigen, and a second binding domain that binds to a second antigen, wherein the first CD4 antigen and the second antigen are not the same. In certain embodiments, a trispecific antibody provided herein comprises a first binding domain comprising a CD4 antibody provided herein that binds to a first CD4 antigen, a second binding domain that binds to a second antigen, and a third binding domain that binds to a third antigen, wherein the first CD4 antigen, the second antigen, and the third antigen are not the same. In certain embodiments, a quadraspecific antibody provided herein comprises a first binding domain comprising a CD4 antibody provided herein that binds to a first CD4 antigen, a second binding domain that binds to a second antigen, a third binding domain that binds to a third antigen, and a fourth binding domain that binds to a fourth antigen, wherein the first CD4 antigen, the second antigen, the third antigen, and the fourth antigen are not the same. In a specific embodiment, a CD4 antibody, or antigen binding fragment thereof, provided herein specifically binds to CD4.


In some embodiments, the multispecific antibody comprises heavy chain variable regions and light chain variable region. In some embodiments, the first binding domain comprises a heavy chain variable region and a light chain variable region. In some embodiments, the second binding domain comprises a heavy chain variable region and a light chain variable region. In some embodiments, the first binding domain comprises a heavy chain variable region and a light chain variable region, and the second binding domain comprises a heavy chain variable region and a light chain variable region. In a some embodiments, the CD4 antibody is not a single domain antibody or nanobody. In some embodiments, the third binding domain comprises a heavy chain variable region and a light chain variable region. In some embodiments, the fourth binding domain comprises a heavy chain variable region and a light chain variable region.


In certain embodiments, the CD4 multispecific antibodies or antigen binding fragments thereof bind to a first epitope located on CD4 and a second epitope of a second target antigen. In some embodiments, provided herein is a multispecific antibody comprising: (a) a first binding domain that binds to a CD4 antigen, and (b) a second binding domain that binds to a second target antigen. In some embodiments, provided herein is a multispecific antibody comprising: (a) a first binding domain that specifically binds to a CD4 antigen, and (b) a second binding domain that specifically binds to a second target antigen. In some embodiments, provided herein is a multispecific antibody comprising: (a) a first binding domain that binds to a first epitope on a CD4 antigen, and (b) a second binding domain that binds to a second epitope on a second target antigen. In some embodiments, provided herein is a multispecific antibody comprising: (a) a first binding domain that specifically binds to a first epitope on a CD4 antigen, and (b) a second binding domain that specifically binds to a second epitope on a second target antigen.


In specific embodiments, the CD4 antigen is on the surface of a T cell. In certain embodiments, the second target antigen is not CD4. The binding of the CD4 multispecific antibody to CD4 present on the surface of the T cell, and the binding of the second target antigen present on the surface of the second target cell can, for example, result in the killing of the second target cell. In other embodiment, the binding of the CD4 multispecific antibody to CD4 present on the surface of the T cell, and the binding of the second target antigen can, for example, result in the activation of the T cell.


In another aspect, provided herein is a multispecific CD4/CD8 antibody. In some embodiments, the multispecific CD4/CD8 antibody is a bispecific antibody. In some embodiments, the multispecific CD4/CD8 antibody is a trispecific antibody. In some embodiments, the multispecific CD4/CD8 antibody is a quadraspecific antibody.


In one embodiment, the multispecific CD4/CD8 antibody comprises: (a) a first binding domain that binds CD8, and (b) a second binding domain that binds to CD4. In one embodiment, the multispecific CD4/CD8 antibody comprises: (a) a first binding domain that binds CD8, and (b) a second binding domain that binds to CD4, and (c) a third binding domain that binds to a third target. In one embodiment, the multispecific CD4/CD8 antibody comprises: (a) a first binding domain that binds CD8, and (b) a second binding domain that binds to CD4, (c) a third binding domain that binds to a third target, and (d) a fourth binding domain that binds to a fourth target.


In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:31; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:32. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:65; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:66. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:99; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:100. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:133; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:134. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:167; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:168. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:201; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:202. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:235; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:236. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:269; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:270. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:303; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:304. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:337; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:338. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:371; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:372. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:405; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:406. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:439; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:440. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:473; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:474. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:507; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:508. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:541; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:542. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:575; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:576. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:609; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:610. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:643; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:644. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:677; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:678. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:711; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:712. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:745; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:746. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:779; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:780. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:813; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:814. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:847; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:848. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:881; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:882. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:915; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:916. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:949; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:950. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:983; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:984. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1017; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1018. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1051; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1052. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1085; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1086. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1119; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1120. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1153; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1154. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1187; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1188. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1221; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1222. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1255; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1256. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1289; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1290. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1323; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1324. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1357; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1358. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1391; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1392. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1425; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1426. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1459; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1460. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1493; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1494. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1527; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1528. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1561; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1562. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1595; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1596. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1629; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1630. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1663; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1664. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1697; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1698. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1731; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1732. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1765; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1766. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1799; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1800. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1833; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1834. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1867; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1868. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1901; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1902. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1935; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1936. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1969; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1970. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2003; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2004. In another aspect, provided herein is an antibody that binds CD8. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2037; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2038. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2071; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2072. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2105; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2106. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2139; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2140. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds CD8 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2173; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2174.


In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the first binding domain that binds CD8 are according to the Kabat numbering system. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the first binding domain that binds CD8 are according to the Chothia numbering system. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the first binding domain that binds CD8 are according to the AbM numbering system. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the first binding domain that binds CD8 are according to the Contact numbering system. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the first binding domain that binds CD8 are according to the IMGT numbering system.


In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the first binding domain binds a CD8 antigen. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the first binding domain binds a CD8 epitope. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the first binding domain specifically binds to CD8. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the first binding domain form a binding site for an antigen of the CD8. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the first binding domain form a binding site for an epitope of the CD8. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the CD8 is present on the surface of a T cell. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the first binding domain binds to CD8α. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the first binding domain binds a CD8α antigen. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds a CD8α epitope. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the first binding domain specifically binds to CD8α. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the first binding domain form a binding site for an antigen of the CD8α. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the first binding domain form a binding site for an epitope of the CD8α. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the CD8α is present on the surface of a T cell. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the first binding domain binds to CD8β. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the first binding domain binds a CD8β antigen. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the first binding domain that binds a CD8β epitope. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the first binding domain specifically binds to CD8β. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the first binding domain form a binding site for an antigen of the CD8β. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the first binding domain form a binding site for an epitope of the CD8β. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the CD8β is present on the surface of a T cell. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the first binding domain binds at the interface of CD8α and CD8β. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the first binding domain binds an antigen at the interface of CD8α and CD8β. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, first binding domain binds an epitope at the interface of CD8α and CD8β. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the first binding domain specifically binds at the interface of CD8α and CD8β. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the first binding domain form a binding site for an antigen at the interface of CD8α and CD8β. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the first binding domain form a binding site for an epitope at the interface of CD8α and CD8β. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the interface of CD8α and CD8β is present on the surface of a T cell.


In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2207; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2208. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2241; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2242. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2275; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2276. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2309; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2310. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2343; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2344. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2377; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2378. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2411; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2412. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2445; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2446. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2479; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2480. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2513; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2514. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2547; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2548. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2581; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2582. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2615; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2616. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2649; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2650. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2683; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2684. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2717; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2718. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2751; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2752. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2785; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2786. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2819; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2820. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2853; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2854. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2887; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2888. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2921; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2922. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2955; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2956. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:2989; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:2990. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3023; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3024. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3057; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3058. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3091; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3092. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3125; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3126. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3159; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3160. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3193; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3194. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3227; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3228. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3261; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3262. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3295; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3296. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3329; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3330. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3363; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3364. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3397; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3398. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3431; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3432. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3465; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3466. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3499; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3500. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3533; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3534. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3567; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3568. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3601; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3602. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3635; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3636. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3669; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3670. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3703; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3704. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3737; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3738. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3771; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3772. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3805; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3806. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3839; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3840. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3873; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3874. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3907; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3908. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3941; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3942. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:3975; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:3976. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4009; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4010. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4043; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4044. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4077; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4078. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4111; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4112. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4145; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4146. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4179; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4180. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4213; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4214. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4247; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4248. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4281; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4282. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4315; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4316. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4349; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4350. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4383; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4384. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4417; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4418. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4451; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4452. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4485; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4486. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4519; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4520. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4553; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4554. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4587; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4588. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4621; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4622. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4655; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4656. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4689; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4690. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4723; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4724. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4757; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4758. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4791; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4792. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4825; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4826. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4859; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4860. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4893; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4894. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4927; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4928. In one embodiment of the multispecific CD4/CD8 antibodies provided herein, the second binding domain that binds CD4 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4961; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4962.


In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the second binding domain that binds CD4 are according to the Kabat numbering system. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the second binding domain that binds CD4 are according to the Chothia numbering system. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the second binding domain that binds CD4 are according to the AbM numbering system. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the second binding domain that binds CD4 are according to the Contact numbering system. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the second binding domain that binds CD4 are according to the IMGT numbering system.


In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the second binding domain binds a CD4 antigen. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the second binding domain binds a CD4 epitope. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the second binding domain specifically binds to CD4. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the second binding domain form a binding site for an antigen of the CD4. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the second binding domain form a binding site for an epitope of the CD4. In some embodiments, the CD4 is present on the surface of a T cell.


In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is not a CD8 antigen. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the fourth target is not a CD8 antigen. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is not a CD8 antigen, and the fourth target is not a CD8 antigen. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is not a CD4 antigen. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the fourth target is not a CD4 antigen. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is not a CD4 antigen, and the fourth target is not a CD4 antigen. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is not a CD8 epitope. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the fourth target is not a CD8 epitope. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is not a CD8 epitope, and the fourth target is not a CD8 epitope. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is not a CD4 epitope. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the fourth target is not a CD4 epitope. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is not a CD4 epitope, and the fourth target is not a CD4 epitope.


In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is a TCR complex. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is CD3. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is CD3ε. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is CD3γ. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is CD3δ. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is CD3ζ. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is a TCRα chain. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is a TCRβ chain. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is a TCRγ chain. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is a TCRδ chain. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is a T cell costimulatory molecule. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is CD28. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is CTLA4. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is ICOS. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is 4-1BB. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is GITR. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is CD27. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is OX40. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is CD40L. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is HVEM. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is Galectin-9. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is TIM-1. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is LFA1. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is CD2. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is PD1.


In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the fourth target is a TCR complex. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the fourth target is CD3. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the fourth target is CD3ε. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the fourth target is CD3γ. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the fourth target is CD3δ. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the fourth target is CD3ζ. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the fourth target is a TCRα chain. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the fourth target is a TCRβ chain. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the fourth target is a TCRγ chain. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the fourth target is a TCRδ chain. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the fourth target is a T cell costimulatory molecule. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the fourth target is CD28. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the fourth target is CTLA4. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the fourth target is ICOS. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the fourth target is 4-1BB. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the fourth target is GITR. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the fourth target is CD27. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the fourth target is OX40. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the fourth target is CD40L. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the fourth target is HVEM. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the fourth target is Galectin-9. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the fourth target is TIM-1. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the fourth target is LFA1. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the fourth target is CD2. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the fourth target is PD1.


In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is a TCR complex, and the fourth target is a T cell costimulatory molecule. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is CD3, and the fourth target is a T cell costimulatory molecule. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is CD3ε, and the fourth target is a T cell costimulatory molecule. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is CD3γ, and the fourth target is a T cell costimulatory molecule. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is CD3δ, and the fourth target is a T cell costimulatory molecule. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is CD3ζ, and the fourth target is a T cell costimulatory molecule. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is a TCRα chain, and the fourth target is a T cell costimulatory molecule. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is a TCRβ chain, and the fourth target is a T cell costimulatory molecule. In some embodiments of the multispecific CD4/CD8 antibodies provided herein, the third target is a TCRγ chain, and the fourth target is a T cell costimulatory molecule. In certain embodiments, the T cell costimulatory molecule is CD28. In certain embodiments, the T cell costimulatory molecule is CTLA4. In certain embodiments, the T cell costimulatory molecule is ICOS. In certain embodiments, the T cell costimulatory molecule is 4-1BB. In certain embodiments, the T cell costimulatory molecule is GITR. In certain embodiments, the T cell costimulatory molecule is CD27. In certain embodiments, the T cell costimulatory molecule is OX40. In certain embodiments, the T cell costimulatory molecule is CD40L. In certain embodiments, the T cell costimulatory molecule is HVEM. In certain embodiments, the T cell costimulatory molecule is Galectin-9. In certain embodiments, the T cell costimulatory molecule is TIM-1. In certain embodiments, the T cell costimulatory molecule is LFA1. In certain embodiments, the T cell costimulatory molecule is CD2. In certain embodiments, the T cell costimulatory molecule is PD1.


In a specific embodiment, the target is from a mammal. In a specific embodiment, the target is from a rat. In a specific embodiment, the target is from a mouse. In a specific embodiment, the target is from a primate. In a specific embodiment, the target is from a human.


In specific embodiments, provided is a multispecific CD4/CD8 antibody in a knob-in-hole format. In specific embodiments, provided is a bispecific CD4/CD8 antibody in a knob-in-hole format. In specific embodiments, provided is a trispecific antibody in a knob-in-hole format. In specific embodiments, provided is a quadraspecific antibody in a knob-in-hole format. Other specificities can be added to an antibody in knob-in-hole format using methods well known in the art (e.g., adding an scFv to the N-terminus or C-terminus). In addition, other formats and methods of making multispecific antibodies are also known in the art and contemplated. In some embodiments, a CD4/CD8 antibody provided herein is comprised in a bispecific antibody. In some embodiments, a CD4/CD8 antibody provided herein is comprised in a trispecific antibody. In some embodiments, a CD4/CD8 antibody provided herein is comprised in a quadraspecific antibody. In some embodiments, a CD4/CD8 bispecific antibody provided herein is comprised in a multispecific antibody.


In certain embodiments, a trispecific CD4/CD8 antibody provided herein comprises a first binding domain comprising a CD8 antibody provided herein that binds to a CD8 epitope, a second binding domain comprising a CD4 antibody provided herein that that binds to a CD4 epitope, and a third binding domain that binds to a third epitope, wherein the CD8 epitope, the CD4 epitope, and the third epitope are not the same. In certain embodiments, a quadraspecific antibody provided herein comprises a first binding domain comprising a CD8 antibody provided herein that binds to a CD8 epitope, a second binding domain comprising a CD4 antibody provided herein that that binds to a CD4 epitope, a third binding domain that binds to a third epitope, and a fourth binding domain that binds to a fourth epitope, wherein the CD8 epitope, the CD4 epitope, the third epitope, and the fourth epitope are not the same. In certain embodiments, a trispecific antibody provided herein comprises a first binding domain comprising a CD8 antibody provided herein that binds to a CD8 antigen, a second binding domain comprising a CD4 antibody provided herein that that binds to a CD4 antigen, and a third binding domain that binds to a third antigen, wherein the CD8 antigen, the CD4 antigen, and the third antigen are not the same. In certain embodiments, a quadraspecific antibody provided herein that binds to a CD8 antigen, a second binding domain comprising a CD4 antibody provided herein that that binds to a CD4 antigen, a third binding domain that binds to a third antigen, and a fourth binding domain that binds to a fourth antigen, wherein the CD8 antigen, the CD4 antigen, the third antigen, and the fourth antigen are not the same. In certain embodiments of a multispecific CD4/CD8 antibody provided herein, the first binding domain that binds to CD8 specifically binds to the CD8. In other embodiments of a multispecific CD4/CD8 antibody provided herein, the second binding domain that binds to CD4 specifically binds to the CD4. In yet other embodiments of a multispecific CD4/CD8 antibody provided herein, the first binding domain that binds to CD8 specifically binds to the CD8, and the second binding domain that binds to CD4 specifically binds to the CD4.


In some embodiments, the multispecific CD4/CD8 antibody comprises heavy chain variable regions and light chain variable region. In some embodiments, the first binding domain comprises a heavy chain variable region and a light chain variable region. In some embodiments, the second binding domain comprises a heavy chain variable region and a light chain variable region. In some embodiments, the first binding domain comprises a heavy chain variable region and a light chain variable region, and the second binding domain comprises a heavy chain variable region and a light chain variable region. In a some embodiments, the CD8 antibody is not a single domain antibody or nanobody. In some embodiments, the third binding domain comprises a heavy chain variable region and a light chain variable region. In some embodiments, the fourth binding domain comprises a heavy chain variable region and a light chain variable region.


In certain embodiments, the CD4/CD8 multispecific antibodies or antigen binding fragments thereof bind to a first epitope located on CD8 and a second epitope of located on CD4. In some embodiments, provided herein is a multispecific CD4/CD8 antibody comprising: (a) a first binding domain that binds to a CD8 antigen, and (b) a second binding domain that binds to a CD4 antigen. In some embodiments, provided herein is a multispecific CD4/CD8 antibody comprising: (a) a first binding domain that specifically binds to a CD8 antigen, and (b) a second binding domain that specifically binds to a CD4 antigen. In some embodiments, provided herein is a multispecific CD4/CD8 antibody comprising: (a) a first binding domain that binds to a first epitope on a CD8 antigen, and (b) a second binding domain that binds to a second epitope on a CD4 antigen. In some embodiments, provided herein is a multispecific antibody comprising: (a) a first binding domain that specifically binds to a first epitope on a CD8 antigen, and (b) a second binding domain that specifically binds to a second epitope on a CD4 antigen.


In specific embodiments, the CD8 antigen is on the surface of a T cell. In specific embodiments, the CD4 antigen is on the surface of a T cell. The binding of the CD4/CD8 multispecific antibody to CD4 and CD8 present on the surface of T cells can, for example, result in the killing of the cell. In other embodiments, the binding of the CD4/CD8 multispecific antibody to CD4 and CD8 present on the surface of T cells can, for example, result in the activation of the T cell.


In some embodiments, a multispecific antibody provided herein is a diabody, a cross-body, or a multispecific antibody obtained via a controlled Fab arm exchange as those described herein.


In some embodiments, the multispecific antibodies include IgG-like molecules with complementary CH3 domains that promote heterodimerization; recombinant IgG-like dual targeting molecules, wherein the two sides of the molecule each contain the Fab fragment or part of the Fab fragment of at least two different antibodies; IgG fusion molecules, wherein full length IgG antibodies are fused to an extra Fab fragment or parts of Fab fragment; Fc fusion molecules, wherein single chain Fv molecules or stabilized diabodies are fused to heavy-chain constant-domains, Fc-regions or parts thereof; Fab fusion molecules, wherein different Fab-fragments are fused together; ScFv- and diabody-based and heavy chain antibodies (e.g., domain antibodies, nanobodies) wherein different single chain Fv molecules or different diabodies or different heavy-chain antibodies (e.g. domain antibodies, nanobodies) are fused to each other or to another protein or carrier molecule.


In some embodiments, IgG-like molecules with complementary CH3 domains molecules include the Triomab/Quadroma (Trion Pharma/Fresenius Biotech), the Knobs-into-Holes (Genentech), CrossMAbs (Roche) and the electrostatically-matched (Amgen), the LUZ-Y (Genentech), the Strand Exchange Engineered Domain body (SEEDbody) (EMD Serono), the Biclonic (Merus) and the DuoBody (Genmab A/S).


In some embodiments, recombinant IgG-like dual targeting molecules include Dual Targeting (DT)-Ig (GSK/Domantis), Two-in-one Antibody (Genentech), Cross-linked Mabs (Karmanos Cancer Center), mAb2 (F-Star) and CovX-body (CovX/Pfizer).


In some embodiments, IgG fusion molecules include Dual Variable Domain (DVD)-Ig (Abbott), IgG-like Bispecific (ImClone/Eli Lilly), Ts2Ab (MedImmune/AZ) and BsAb (Zymogenetics), HERCULES (Biogen Idec) and TvAb (Roche).


In some embodiments, Fc fusion molecules can include ScFv/Fc Fusions (Academic Institution), SCORPION (Emergent BioSolutions/Trubion, Zymogenetics/BMS), Dual Affinity Retargeting Technology (Fc-DART) (MacroGenics) and Dual (ScFv)2-Fab (National Research Center for Antibody Medicine—China).


In some embodiments, Fab fusion bispecific antibodies include F(ab)2 (Medarex/AMGEN), Dual-Action or Bis-Fab (Genentech), Dock-and-Lock (DNL) (ImmunoMedics), Bivalent Bispecific (Biotecnol) and Fab-Fv (UCB-Celltech). ScFv-, diabody-based, and domain antibodies, include but are not limited to, Bispecific T Cell Engager (BiTE) (Micromet), Tandem Diabody (Tandab) (Affimed), Dual Affinity Retargeting Technology (DART) (MacroGenics), Single-chain Diabody (Academic), TCR-like Antibodies (AIT, ReceptorLogics), Human Serum Albumin ScFv Fusion (Merrimack) and COMBODY (Epigen Biotech), dual targeting nanobodies (Ablynx), dual targeting heavy chain only domain antibodies.


Full length bispecific antibodies provided herein can be generated for example using Fab arm exchange (or half molecule exchange) between two mono specific bivalent antibodies by introducing substitutions at the heavy chain CH3 interface in each half molecule to favor heterodimer formation of two antibody half molecules having distinct specificity either in vitro in cell-free environment or using co-expression. The Fab arm exchange reaction is the result of a disulfide-bond isomerization reaction and dissociation-association of CH3 domains. The heavy-chain disulfide bonds in the hinge regions of the parent mono specific antibodies are reduced. The resulting free cysteines of one of the parent monospecific antibodies form an inter heavy-chain disulfide bond with cysteine residues of a second parent mono specific antibody molecule and simultaneously CH3 domains of the parent antibodies release and reform by dissociation-association. The CH3 domains of the Fab arms can be engineered to favor heterodimerization over homodimerization. The resulting product is a bispecific antibody having two Fab arms or half molecules which each binding a distinct epitope, e.g., an epitope on CD8 and an epitope on CD4. Other methods of making multispecific antibodies are known and contemplated.


“Homodimerization” as used herein refers to an interaction of two heavy chains having identical CH3 amino acid sequences. “Homodimer” as used herein refers to an antibody having two heavy chains with identical CH3 amino acid sequences.


“Heterodimerization” as used herein refers to an interaction of two heavy chains having non-identical CH3 amino acid sequences. “Heterodimer” as used herein refers to an antibody having two heavy chains with non-identical CH3 amino acid sequences.


The “knob-in-hole” strategy (see, e.g., PCT Publ. No. WO2006/028936) can be used to generate full length bispecific antibodies. Briefly, selected amino acids forming the interface of the CH3 domains in human IgG can be mutated at positions affecting CH3 domain interactions to promote heterodimer formation. An amino acid with a small side chain (hole) is introduced into a heavy chain of an antibody specifically binding a first antigen and an amino acid with a large side chain (knob) is introduced into a heavy chain of an antibody specifically binding a second antigen. After co-expression of the two antibodies, a heterodimer is formed as a result of the preferential interaction of the heavy chain with a “hole” with the heavy chain with a “knob.” Exemplary CH3 substitution pairs forming a knob and a hole are (expressed as modified position in the first CH3 domain of the first heavy chain/modified position in the second CH3 domain of the second heavy chain): T366Y/F405A, T366W/F405W, F405W/Y407A, T394W/Y407T, T394S/Y407A, T366W/T394S, F405W/T394S and T366W/T366S_L368A_Y407V.


Other strategies such as promoting heavy chain heterodimerization using electrostatic interactions by substituting positively charged residues at one CH3 surface and negatively charged residues at a second CH3 surface can be used, as described in US Pat. Publ. No. US2010/0015133; US Pat. Publ. No. US2009/0182127; US Pat. Publ. No. US2010/028637; or US Pat. Publ. No. US2011/0123532. In other strategies, heterodimerization can be promoted by the following substitutions (expressed as modified position in the first CH3 domain of the first heavy chain/modified position in the second CH3 domain of the second heavy chain): L351Y_F405AY407V/T394W, T366I_K392M_T394W/F405A_Y407V, T366L_K392M_T394W/F405A_Y407V, L351Y_Y407A/T366A_K409F, L351Y_Y407A/T366V K409F Y407A/T366A_K409F, or T350V_L351Y_F405A Y407V/T350V_T366L_K392L_T394W as described in U.S. Pat. Publ. No. US2012/0149876 or U.S. Pat. Publ. No. US2013/0195849.


In addition to methods described above, bispecific antibodies provided herein can be generated in vitro in a cell-free environment by introducing asymmetrical mutations in the CH3 regions of two mono specific homodimeric antibodies and forming the bispecific heterodimeric antibody from two parent monospecific homodimeric antibodies in reducing conditions to allow disulfide bond isomerization according to methods described in PCT Pat. Publ. No. WO2011/131746. In the methods, the first monospecific bivalent antibody and the second monospecific bivalent antibody are engineered to have certain substitutions at the CH3 domain that promotes heterodimer stability; the antibodies are incubated together under reducing conditions sufficient to allow the cysteines in the hinge region to undergo disulfide bond isomerization; thereby generating the bispecific antibody by Fab arm exchange. The incubation conditions can optionally be restored to non-reducing conditions. Exemplary reducing agents that can be used are 2-mercaptoethylamine (2-MEA), dithiothreitol (DTT), dithioerythritol (DTE), glutathione, tris (2-carboxyethyl) phosphine (TCEP), L-cysteine and beta-mercaptoethanol, preferably a reducing agent selected from the group consisting of: 2-mercaptoethylamine, dithiothreitol and tris (2-carboxyethyl) phosphine. For example, incubation for at least 90 min at a temperature of at least 20° C. in the presence of at least 25 mM 2-MEA or in the presence of at least 0.5 mM dithiothreitol at a pH from 5-8, for example at pH of 7.0 or at pH of 7.4 can be used.


In some embodiments, the CD8 multispecific antibody comprises a single chain antibody. In some embodiments, the CD8 multispecific antibody comprises a single domain antibody. In certain embodiments, the CD8 multispecific antibody comprises a nanobody. In certain embodiments, the CD8 multispecific antibody comprises a VHH antibody. In certain embodiments, the CD8 multispecific antibody comprises a llama antibody. In some embodiments, the CD8 multispecific antibody does not comprise a single chain antibody. In some embodiments, the CD8 multispecific antibody does not comprise a single domain antibody. In certain embodiments, the CD8 multispecific antibody does not comprise a nanobody. In certain embodiments, the CD8 multispecific antibody does not comprise a VHH antibody. In certain embodiments, the CD8 multispecific antibody does not comprise a llama antibody.


According to another particular aspect, provided herein is a CD8 antibody or antigen-binding fragment thereof that induces antibody-dependent cell-mediated cytotoxicity (ADCC). The antibody or antigen-binding fragment thereof can, for example, induce ADCC in vitro.


In certain embodiments, the antibody or antigen-binding fragment thereof induces T cell dependent cytotoxicity of a second cell in vitro with an EC50 of less than about 160 pM, when assessed in vitro at an effector to target cell ratio of 1:1.


In some embodiments, CD8 is present on the surface of a T cell. In some embodiments, the CD8 is present on the surface of a T cell, and the second target antigen is on the surface of a second cell. In some embodiments, the second cell is killed when the multispecific antibody binds to the CD8 on the surface of the T cell and the second target antigen on the surface of the second cell.


In some embodiments, the multispecific antibody induces T cell dependent cytotoxicity of the second cell in vitro with an EC50 of less than about 500 pM. In some embodiments, the multispecific antibody induces T cell dependent cytotoxicity of the second cell in vitro with an EC50 of less than about 300 pM. In some embodiments, the multispecific antibody induces γδ T cell dependent cytotoxicity of the second cell in vitro with an EC50 of less than about 160 pM. In some embodiments, the EC50 is assessed with a mixture of γδ T effector cells and target cells expressing the second target antigen. In some embodiments, the effector cell to target cell ratio is about 0.01 to 1 to about 5 to 1. In some embodiments, the effector cell to target cell ratio is about 0.1 to 1 to about 2 to 1. In some embodiments, the effector cell to target cell ratio is about 1:1.


In certain embodiments, the EC50 is less than about 1000 pM, less than about 900 pM, less than about 800 pM, less than about 700 pM, less than about 600 pM, less than about 500 pM, less than about 400 pM, less than about 300 pM, less than about 200 pM, less than about 190 pM, less than about 180 pM, less than about 170 pM, less than about 160 pM, less than about 150 pM, less than about 140 pM, less than about 130 pM, less than about 120 pM, less than about 110 pM, less than about 100 pM, less than about 90 pM, less than about 80 pM, less than about 70 pM, less than about 60 pM, less than about 50 pM, less than about 40 pM, less than about 30 pM, less than about 20 pM, or less than about 10 pM.


In certain embodiments, the effector to target cell ratio can, for example, be 0.01:1, 0.02:1, 0.03:1, 0.04:1, 0.05:1, 0.06:1, 0.07:1, 0.08:1, 0.09:1, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, or 10:1. In certain embodiments, the concentration of the multispecific antibody or antigen-binding fragment thereof is about 0.000005 ng/mL, about 0.00005 ng/mL, about 0.0005, about 0.005 ng/mL, about 0.01 ng/mL, about 0.02 ng/mL, about 0.03 ng/mL, about 0.04 ng/mL, about 0.05 ng/mL, about 0.06 ng/mL, about 0.07 ng/mL, about 0.08 ng/mL, about 0.09 ng/mL, about 0.1 ng/mL, about 0.5 ng/mL, about 1.0 ng/mL, about 10 ng/mL, about 20 ng/mL about, about 30 ng/mL about 40 ng/mL, about 50 ng/mL, about 60 ng/mL, about 70 ng/mL, about 80 ng/mL, about 90 ng/mL, about 100 ng/mL, or about 1000 ng/mL.


In another aspect, provided herein is an antibody that competes for binding to CD8 with any of the CD8 antibodies described herein. In another aspect, provided herein is an antibody that binds to the same epitope as any of the CD8 antibodies described herein. In another aspect, provided is a CD8 antibody that binds an epitope on CD8 that overlaps with the epitope on CD8 bound by a CD8 antibody described herein. In some embodiments, the CD8 antibody comprises a VH CDR1, VH CDR2, and VH CDR3 of a CD8 antibody provided herein. In some embodiments, the CD8 antibody comprises a VL CDR1, VL CDR2, and VL CDR3 of a CD8 antibody provided herein. In some embodiments, the CD8 antibody comprises a VH CDR1, VH CDR2, VH CDR3, a VL CDR1, VL CDR2, and VL CDR3 of a CD8 antibody provided herein. In some embodiments, the CD8 antibody comprises a VH of a CD8 antibody provided herein. In some embodiments, the CD8 antibody comprises a VL of a CD8 antibody provided herein. In some embodiments, the CD8 antibody comprises a VH and a VL of a CD8 antibody provided herein. In some embodiments, the CD8 antibody comprises a VH CDR1, VH CDR2, VH CDR3, a VL CDR1, VL CDR2, and VL CDR3 of a CD8 antibody provided herein. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the CD8 antibody are according to the Kabat numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the CD8 antibody are according to the Chothia numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the CD8 antibody are according to the AbM numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the CD8 antibody are according to the Contact numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the CD8 antibody are according to the IMGT numbering system. In certain embodiments, the CD8 antibody is a multispecific antibody. In some embodiments, the CD8 antibody is a bispecific antibody.


In another aspect, provided is an antibody that competes for binding to CD8 with a CD8 reference antibody. In another aspect, provided is a CD8 antibody that binds to the same CD8 epitope as a CD8 reference antibody. In another aspect, provided is a CD8 antibody that binds an epitope on CD8 that overlaps with the epitope on CD8 bound by a CD8 reference antibody. In some embodiments, the CD8 reference antibody comprises a VH CDR1, VH CDR2, and VH CDR3 of a CD8 reference antibody provided herein. In some embodiments, the CD8 reference antibody comprises a VL CDR1, VL CDR2, and VL CDR3 of a CD8 reference antibody provided herein. In some embodiments, the CD8 reference antibody comprises a VH CDR1, VH CDR2, VH CDR3, a VL CDR1, VL CDR2, and VL CDR3 of a CD8 reference antibody provided herein. In some embodiments, the CD8 reference antibody comprises a VH of a CD8 reference antibody provided herein. In some embodiments, the CD8 reference antibody comprises a VL of a CD8 reference antibody provided herein. In some embodiments, the CD8 reference antibody comprises a VH and a VL of a CD8 reference antibody provided herein. In some embodiments, the CD8 reference antibody comprises a VH CDR1, VH CDR2, VH CDR3, a VL CDR1, VL CDR2, and VL CDR3 of a CD8 reference antibody provided herein. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the CD8 reference antibody are according to the Kabat numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the CD8 reference antibody are according to the Chothia numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the CD8 reference antibody are according to the AbM numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the CD8 reference antibody are according to the Contact numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the CD8 reference antibody are according to the IMGT numbering system. In certain embodiments, the antibody is a multispecific antibody. In some embodiments, the antibody is a bispecific antibody. In certain embodiments, the CD8 reference antibody is a multispecific antibody. In some embodiments, the CD8 reference antibody is a bispecific antibody.


The disclosure also provides an isolated multispecific antibody, comprising: a first half molecule and a second half molecule, wherein the first half molecule comprises a first antigen binding domain and a second antigen binding domain and the second half molecule comprises a third antigen binding domain, wherein the first antigen binding domain specifically binds CD8, the second antigen binding domain specifically binds a second target, and the third antigen binding domain specifically binds a third target. In certain embodiments, the second target is a TCR complex. In some embodiments, the multispecific antibody activates or recruits CD8+ CTLs upon co-engagement of the TCR complex and CD8. In some embodiments, the multispecific antibody is unable to activate or recruit CD8+ CTLs in the absence of co-engagement of the TCR complex and CD8. In some embodiments, the multispecific antibody specifically binds CD8 and the TCR complex with an affinity that results in activation or recruitment of CD8+ CTL only upon co-engagement of the TCR complex and CD8.


In some embodiments, the CD4 multispecific antibody comprises a single chain antibody. In some embodiments, the CD4 multispecific antibody comprises a single domain antibody. In certain embodiments, the CD4 multispecific antibody comprises a nanobody. In certain embodiments, the CD4 multispecific antibody comprises a VHH antibody. In certain embodiments, the CD4 multispecific antibody comprises a llama antibody. In some embodiments, the CD4 multispecific antibody does not comprise a single chain antibody. In some embodiments, the CD4 multispecific antibody does not comprise a single domain antibody. In certain embodiments, the CD4 multispecific antibody does not comprise a nanobody. In certain embodiments, the CD4 multispecific antibody does not comprise a VHH antibody. In certain embodiments, the CD4 multispecific antibody does not comprise a llama antibody.


According to another particular aspect, provided herein is a CD4 antibody or antigen-binding fragment thereof that induces antibody-dependent cell-mediated cytotoxicity (ADCC). The antibody or antigen-binding fragment thereof can, for example, induce ADCC in vitro.


In certain embodiments, the antibody or antigen-binding fragment thereof induces T cell dependent cytotoxicity of a second cell in vitro with an EC50 of less than about 160 pM, when assessed in vitro at an effector to target cell ratio of 1:1.


In some embodiments, CD4 is present on the surface of a T cell. In some embodiments, the CD4 is present on the surface of a T cell, and the second target antigen is on the surface of a second cell. In some embodiments, the second cell is killed when the multispecific antibody binds to the CD4 on the surface of the T cell and the second target antigen on the surface of the second cell. In some embodiments, the multispecific antibody induces T cell dependent cytotoxicity of the second cell in vitro with an EC50 of less than about 500 pM. In some embodiments, the multispecific antibody induces T cell dependent cytotoxicity of the second cell in vitro with an EC50 of less than about 300 pM. In some embodiments, the multispecific antibody induces γδ T cell dependent cytotoxicity of the second cell in vitro with an EC50 of less than about 160 pM. In some embodiments, the EC50 is assessed with a mixture of γδ T effector cells and target cells expressing the second target antigen. In some embodiments, the effector cell to target cell ratio is about 0.01 to 1 to about 5 to 1. In some embodiments, the effector cell to target cell ratio is about 0.1 to 1 to about 2 to 1. In some embodiments, the effector cell to target cell ratio is about 1:1.


In certain embodiments, the EC50 is less than about 1000 pM, less than about 900 pM, less than about 800 pM, less than about 700 pM, less than about 600 pM, less than about 500 pM, less than about 400 pM, less than about 300 pM, less than about 200 pM, less than about 190 pM, less than about 180 pM, less than about 170 pM, less than about 160 pM, less than about 150 pM, less than about 140 pM, less than about 130 pM, less than about 120 pM, less than about 110 pM, less than about 100 pM, less than about 90 pM, less than about 80 pM, less than about 70 pM, less than about 60 pM, less than about 50 pM, less than about 40 pM, less than about 30 pM, less than about 20 pM, or less than about 10 pM.


In certain embodiments, the effector to target cell ratio can, for example, be 0.01:1, 0.02:1, 0.03:1, 0.04:1, 0.05:1, 0.06:1, 0.07:1, 0.08:1, 0.09:1, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, or 10:1.


In certain embodiments, the concentration of the multispecific antibody or antigen-binding fragment thereof is about 0.000005 ng/mL, about 0.00005 ng/mL, about 0.0005, about 0.005 ng/mL, about 0.01 ng/mL, about 0.02 ng/mL, about 0.03 ng/mL, about 0.04 ng/mL, about 0.05 ng/mL, about 0.06 ng/mL, about 0.07 ng/mL, about 0.08 ng/mL, about 0.09 ng/mL, about 0.1 ng/mL, about 0.5 ng/mL, about 1.0 ng/mL, about 10 ng/mL, about 20 ng/mL about, about 30 ng/mL about 40 ng/mL, about 50 ng/mL, about 60 ng/mL, about 70 ng/mL, about 80 ng/mL, about 90 ng/mL, about 100 ng/mL, or about 1000 ng/mL.


In another aspect, provided herein is an antibody that competes for binding to CD4 with any of the CD4 antibodies described herein. In another aspect, provided herein is an antibody that binds to the same epitope as any of the CD4 antibodies described herein. In another aspect, provided is a CD4 antibody that binds an epitope on CD4 that overlaps with the epitope on CD4 bound by a CD4 antibody described herein. In some embodiments, the CD4 antibody comprises a VH CDR1, VH CDR2, and VH CDR3 of a CD4 antibody provided herein. In some embodiments, the CD4 antibody comprises a VL CDR1, VL CDR2, and VL CDR3 of a CD4 antibody provided herein. In some embodiments, the CD4 antibody comprises a VH CDR1, VH CDR2, VH CDR3, a VL CDR1, VL CDR2, and VL CDR3 of a CD4 antibody provided herein. In some embodiments, the CD4 antibody comprises a VH of a CD4 antibody provided herein. In some embodiments, the CD4 antibody comprises a VL of a CD4 antibody provided herein. In some embodiments, the CD4 antibody comprises a VH and a VL of a CD4 antibody provided herein. In some embodiments, the CD4 antibody comprises a VH CDR1, VH CDR2, VH CDR3, a VL CDR1, VL CDR2, and VL CDR3 of a CD4 antibody provided herein. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the CD4 antibody are according to the Kabat numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the CD4 antibody are according to the Chothia numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the CD4 antibody are according to the AbM numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the CD4 antibody are according to the Contact numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the CD4 antibody are according to the IMGT numbering system. In certain embodiments, the CD4 antibody is a multispecific antibody. In some embodiments, the CD4 antibody is a bispecific antibody.


In another aspect, provided is an antibody that competes for binding to CD4 with a CD4 reference antibody. In another aspect, provided is a CD4 antibody that binds to the same CD4 epitope as a CD4 reference antibody. In another aspect, provided is a CD4 antibody that binds an epitope on CD4 that overlaps with the epitope on CD4 bound by a CD4 reference antibody. In some embodiments, the CD4 reference antibody comprises a VH CDR1, VH CDR2, and VH CDR3 of a CD4 reference antibody provided herein. In some embodiments, the CD4 reference antibody comprises a VL CDR1, VL CDR2, and VL CDR3 of a CD4 reference antibody provided herein. In some embodiments, the CD4 reference antibody comprises a VH CDR1, VH CDR2, VH CDR3, a VL CDR1, VL CDR2, and VL CDR3 of a CD4 reference antibody provided herein. In some embodiments, the CD4 reference antibody comprises a VH of a CD4 reference antibody provided herein. In some embodiments, the CD4 reference antibody comprises a VL of a CD4 reference antibody provided herein. In some embodiments, the CD4 reference antibody comprises a VH and a VL of a CD4 reference antibody provided herein. In some embodiments, the CD4 reference antibody comprises a VH CDR1, VH CDR2, VH CDR3, a VL CDR1, VL CDR2, and VL CDR3 of a CD4 reference antibody provided herein. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the CD4 reference antibody are according to the Kabat numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the CD4 reference antibody are according to the Chothia numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the CD4 reference antibody are according to the AbM numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the CD4 reference antibody are according to the Contact numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the CD4 reference antibody are according to the IMGT numbering system. In certain embodiments, the antibody is a multispecific antibody. In some embodiments, the antibody is a bispecific antibody. In certain embodiments, the CD4 reference antibody is a multispecific antibody. In some embodiments, the CD4 reference antibody is a bispecific antibody.


The disclosure also provides an isolated multispecific antibody, comprising: a first half molecule and a second half molecule, wherein the first half molecule comprises a first antigen binding domain and a second antigen binding domain and the second half molecule comprises a third antigen binding domain, wherein the first antigen binding domain specifically binds CD4, the second antigen binding domain specifically binds a second target, and the third antigen binding domain specifically binds a third target. In certain embodiments, the second target is a TCR complex. In some embodiments, the multispecific antibody activates or recruits CD4+ T cells upon co-engagement of the TCR complex and CD4. In some embodiments, the multispecific antibody is unable to activate or recruit CD4+ T cells in the absence of co-engagement of the TCR complex and CD4. In some embodiments, the multispecific antibody specifically binds CD4 and the TCR complex with an affinity that results in activation or recruitment of CD4+ T cells only upon co-engagement of the TCR complex and CD4.


In some embodiments described herein, immune effector properties of the antibodies provided herein can be enhanced or silenced through Fc modifications by techniques known to those skilled in the art. For example, Fc effector functions such as Clq binding, complement dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP), down regulation of cell surface receptors (e.g., B cell receptor; BCR), etc. can be provided and/or controlled by modifying residues in the Fc responsible for these activities.


“Antibody-dependent cell-mediated cytotoxicity” or “ADCC” refers to a cell-mediated reaction in which non-specific cytotoxic cells that express Fc receptors (FcRs) (e.g. Natural Killer (NK) cells, neutrophils, and macrophages) recognize bound antibody on a target cell and subsequently cause lysis of the target cell.


The ability of antibodies to induce ADCC can be enhanced by engineering their oligosaccharide component. Human IgG1 or IgG3 are N-glycosylated at Asn297 with the majority of the glycans in the well-known biantennary G0, G0F, G1, G1F, G2 or G2F forms. Antibodies produced by non-engineered CHO cells typically have a glycan fucose content of about at least 85%. The removal of the core fucose from the biantennary complex-type oligosaccharides attached to the Fc regions enhances the ADCC of antibodies via improved FcγRIIIa binding without altering antigen binding or CDC activity. Such Abs can be achieved using different methods reported to lead to the successful expression of relatively high defucosylated antibodies bearing the biantennary complex-type of Fc oligosaccharides such as control of culture osmolality (Konno et al., Cytotechnology 64:249-65, 2012), application of a variant CHO line Lec13 as the host cell line (Shields et al., J Biol Chem 277:26733-26740, 2002), application of a variant CHO line EB66 as the host cell line (Olivier et al., MAbs; 2(4), 2010; Epub ahead of print; PMID:20562582), application of a rat hybridoma cell line YB2/0 as the host cell line (Shinkawa et al., J Biol Chem 278:3466-3473, 2003), introduction of small interfering RNA specifically against the α-1,6-fucosyltrasferase (FUT8) gene (Mori et al., Biotechnol Bioeng 88:901-908, 2004), or coexpression of β-1,4-N-acetylglucosaminyltransferase III and golgi α-mannosidase II or a potent alpha-mannosidase I inhibitor, kifunensine (Ferrara et al., J Biol Chem 281:5032-5036, 2006, Ferrara et al., Biotechnol Bioeng 93:851-861, 2006; Xhou et al., Biotechnol Bioeng 99:652-65, 2008).


In some embodiments described herein, ADCC elicited by the antibodies provided herein can also be enhanced by certain substitutions in the antibody Fc. Exemplary substitutions are for example substitutions at amino acid positions 256, 290, 298, 312, 356, 330, 333, 334, 360, 378 or 430 (residue numbering according to the EU index) as described in U.S. Pat. No. 6,737,056.


In some embodiments, a CD8 antibody provided herein is chimeric. In some embodiments, a CD8 antibody provided herein is human. In some embodiments, a CD8 antibody provided herein is humanized. In certain embodiments, a CD8 antibody provided herein is an isolated CD8 antibody. In some embodiments, a CD8 antigen binding fragment provided herein is chimeric. In some embodiments, a CD8 antigen binding fragment provided herein is human. In some embodiments, a CD8 antigen binding fragment provided herein is humanized. In certain embodiments, a CD8 antigen binding fragment provided herein is an isolated CD8 antigen binding fragment. In some embodiments, a CD8 antibody provided herein is an IgG antibody. In some embodiments, the IgG antibody is an IgG1 antibody. In some embodiments, the IgG antibody is an IgG2 antibody. In some embodiments, the IgG antibody is an IgG3 antibody. In some embodiments, the IgG antibody is an IgG4 antibody. In some embodiments, a CD8 antibody provided herein is multivalent. In some embodiments, the antibody is capable of binding at least three antigens. In some embodiments, the antibody is capable of binding at least five antigens.


In some embodiments, a CD8 multispecific antibody provided herein is chimeric. In some embodiments, a CD8 multispecific antibody provided herein is human. In some embodiments, a CD8 multispecific antibody provided herein is humanized. In certain embodiments, a CD8 multispecific antibody provided herein is an isolated CD8 multispecific antibody. In some embodiments, a CD8 multispecific antibody comprising a CD8 antigen binding fragment provided herein is chimeric. In some embodiments, a CD8 multispecific antibody comprising a CD8 antigen binding fragment provided herein is human. In some embodiments, a CD8 multispecific antibody comprising a CD8 antigen binding fragment provided herein is humanized. In certain embodiments, a CD8 multispecific antibody comprising a CD8 antigen binding fragment provided herein is an isolated CD8 multispecific antibody. In certain embodiments, the CD8 multispecific antibody is a multispecific CD4/CD8 antibody.


In some embodiments of the CD8 multispecific antibodies provided herein, the first binding domain is human. In some embodiments, the second binding domain is human. In some embodiments of the CD8 multispecific antibodies provided herein, both the first binding domain and the second binding domain are human. In some embodiments of the CD8 multispecific antibodies provided herein, the first binding domain is humanized. In some embodiments of the CD8 multispecific antibodies provided herein, the second binding domain is humanized. In some embodiments of the CD8 multispecific antibodies provided herein, both the first binding domain and the second binding domain are humanized. In some embodiments of the CD8 multispecific antibodies provided herein, both the first binding domain is human and the second binding domain is humanized. In some embodiments of the CD8 multispecific antibodies provided herein, both the first binding domain is humanized and the second binding domain is human. In certain embodiments, the CD8 multispecific antibody is a multispecific CD4/CD8 antibody.


In some embodiments, a CD8 multispecific antibody provided herein is multivalent. In some embodiments, the multispecific antibody is capable of binding at least three antigens. In some embodiments, the multispecific antibody is capable of binding at least five antigens. In certain embodiments, the multispecific antibody is a multispecific antibody. In some embodiments, a CD8 multispecific antibody provided herein is an IgG antibody. In some embodiments, the IgG antibody is an IgG1 antibody. In some embodiments, the IgG antibody is an IgG2 antibody. In some embodiments, the IgG antibody is an IgG3 antibody. In some embodiments, the IgG antibody is an IgG4 antibody. In certain embodiments, the CD8 multispecific antibody is a multispecific CD4/CD8 antibody.


In certain embodiments, CD8 antibodies provided herein are part of a multispecific antibody. In some embodiments, the multispecific antibody comprises a first binding domain that binds to a CD8 antigen. In some embodiments, the multispecific antibody comprises a first binding domain that binds to a CD8 antigen and comprises a second binding domain that binds to a second target antigen, as provided herein. In certain embodiments, the multispecific antibody binds to a CD8 antigen, a second target antigen, and one or more additional antigens. In some embodiments of the various antibodies provided herein, the antibody binds to an epitope of a given antigen. In certain embodiments, the multispecific CD8 antibody is a multispecific CD4/CD8 antibody, wherein the second target is CD4.


In some embodiments, a CD4 antibody provided herein is chimeric. In some embodiments, a CD4 antibody provided herein is human. In some embodiments, a CD4 antibody provided herein is humanized. In certain embodiments, a CD4 antibody provided herein is an isolated CD4 antibody. In some embodiments, a CD4 antigen binding fragment provided herein is chimeric. In some embodiments, a CD4 antigen binding fragment provided herein is human. In some embodiments, a CD4 antigen binding fragment provided herein is humanized. In certain embodiments, a CD4 antigen binding fragment provided herein is an isolated CD4 antigen binding fragment. In some embodiments, a CD4 antibody provided herein is an IgG antibody. In some embodiments, the IgG antibody is an IgG1 antibody. In some embodiments, the IgG antibody is an IgG2 antibody. In some embodiments, the IgG antibody is an IgG3 antibody. In some embodiments, the IgG antibody is an IgG4 antibody. In some embodiments, a CD4 antibody provided herein is multivalent. In some embodiments, the antibody is capable of binding at least three antigens. In some embodiments, the antibody is capable of binding at least five antigens.


In some embodiments, a CD4 multispecific antibody provided herein is chimeric. In some embodiments, a CD4 multispecific antibody provided herein is human. In some embodiments, a CD4 multispecific antibody provided herein is humanized. In certain embodiments, a CD4 multispecific antibody provided herein is an isolated CD4 multispecific antibody. In some embodiments, a CD4 multispecific antibody comprising a CD4 antigen binding fragment provided herein is chimeric. In some embodiments, a CD4 multispecific antibody comprising a CD4 antigen binding fragment provided herein is human. In some embodiments, a CD4 multispecific antibody comprising a CD4 antigen binding fragment provided herein is humanized. In certain embodiments, a CD4 multispecific antibody comprising a CD4 antigen binding fragment provided herein is an isolated CD4 multispecific antibody. In certain embodiments, the CD4 multispecific antibody is a multispecific CD4/CD8 antibody.


In some embodiments of the CD4 multispecific antibodies provided herein, the first binding domain is human. In some embodiments, the second binding domain is human. In some embodiments of the CD4 multispecific antibodies provided herein, both the first binding domain and the second binding domain are human. In some embodiments of the CD4 multispecific antibodies provided herein, the first binding domain is humanized. In some embodiments of the CD4 multispecific antibodies provided herein, the second binding domain is humanized. In some embodiments of the CD4 multispecific antibodies provided herein, both the first binding domain and the second binding domain are humanized. In some embodiments of the CD4 multispecific antibodies provided herein, both the first binding domain is human and the second binding domain is humanized. In some embodiments of the CD4 multispecific antibodies provided herein, both the first binding domain is humanized and the second binding domain is human. In certain embodiments, the CD4 multispecific antibody is a multispecific CD4/CD8 antibody.


In some embodiments, a CD4 multispecific antibody provided herein is multivalent. In some embodiments, the multispecific antibody is capable of binding at least three antigens. In some embodiments, the multispecific antibody is capable of binding at least five antigens. In certain embodiments, the multispecific antibody is a multispecific antibody. In some embodiments, a CD4 multispecific antibody provided herein is an IgG antibody. In some embodiments, the IgG antibody is an IgG1 antibody. In some embodiments, the IgG antibody is an IgG2 antibody. In some embodiments, the IgG antibody is an IgG3 antibody. In some embodiments, the IgG antibody is an IgG4 antibody. In certain embodiments, the CD4 multispecific antibody is a multispecific CD4/CD8 antibody.


In certain embodiments, CD4 antibodies provided herein are part of a multispecific antibody. In some embodiments, the multispecific antibody comprises a first binding domain that binds to a CD4 antigen. In some embodiments, the multispecific antibody comprises a first binding domain that binds to a CD4 antigen and comprises a second binding domain that binds to a second target antigen, as provided herein. In certain embodiments, the multispecific antibody binds to a CD4 antigen, a second target antigen, and one or more additional antigens. In some embodiments of the various antibodies provided herein, the antibody binds to an epitope of a given antigen. In certain embodiments, the multispecific CD8 antibody is a multispecific CD4/CD8 antibody, wherein the second target is CD8.


Also provided is a nucleic acid encoding an antibody provided herein. In another general aspect, provide is a vector comprising an isolated nucleic acid encoding an antibody provided herein. In another general aspect, provided is a vector comprising an isolated nucleic acid encoding an antibody provided herein. Also provided is a vector comprising a nucleic acid encoding an antibody provided herein. Also provided is a host cell comprising a vector comprising a nucleic acid encoding an antibody provided herein. Also provided is a kit comprising the vector comprising a nucleic acid encoding an antibody provided herein, and packaging for the same. In another general aspect, provided herein is an isolated nucleic acid encoding a monoclonal antibody or antigen-binding fragment thereof provided herein.


In certain embodiments, the antibody is a CD8 antibody. In some embodiments, the antibody is a CD4 antibody. In certain embodiments, the antibody is a multispecific CD8 antibody. In some embodiments, the antibody is a multispecific CD4 antibody. In some embodiments, the antibody is a multispecific CD4/CD8 antibody.


Also provided is a nucleic acid encoding a multispecific antibody that binds to a CD8 provided herein. In another general aspect, provide is a vector comprising an isolated nucleic acid encoding a CD8 multispecific antibody provided herein. In another general aspect, provided is a vector comprising an isolated nucleic acid encoding a CD8 multispecific antibody provided herein. Also provided is a vector comprising a nucleic acid encoding a multispecific antibody that binds to CD8 provided herein. Also provided is a host cell comprising a vector comprising a nucleic acid encoding a multispecific antibody that binds to CD8 provided herein. Also provided is a kit comprising the vector comprising a nucleic acid encoding a multispecific antibody that binds to CD8 provided herein, and packaging for the same. Also provided is an isolated nucleic acid encoding a monoclonal antibody provided herein. Also provided is an isolated nucleic acid encoding an antigen binding fragment provided herein. Also provided is a nucleic acid encoding a multispecific antibody comprising: (a) a first binding domain that binds to CD8, and (b) a second binding domain that binds to a second target that is not CD8, as provided herein.


Also provided is a nucleic acid encoding a multispecific antibody that binds to a CD4 provided herein. In another general aspect, provide is a vector comprising an isolated nucleic acid encoding a CD4 multispecific antibody provided herein. In another general aspect, provided is a vector comprising an isolated nucleic acid encoding a CD4 multispecific antibody provided herein. Also provided is a vector comprising a nucleic acid encoding a multispecific antibody that binds to CD4 provided herein. Also provided is a host cell comprising a vector comprising a nucleic acid encoding a multispecific antibody that binds to CD4 provided herein. Also provided is a kit comprising the vector comprising a nucleic acid encoding a multispecific antibody that binds to CD4 provided herein, and packaging for the same. Also provided is an isolated nucleic acid encoding a monoclonal antibody provided herein. Also provided is an isolated nucleic acid encoding an antigen binding fragment provided herein. Also provided is a nucleic acid encoding a multispecific antibody comprising: (a) a first binding domain that binds to CD4, and (b) a second binding domain that binds to a second target that is not CD4, as provided herein.


Also provided is a nucleic acid encoding a multispecific CD4/CD8 antibody provided herein. In another general aspect, provide is a vector comprising an isolated nucleic acid encoding a multispecific CD4/CD8 antibody provided herein. In another general aspect, provided is a vector comprising an isolated nucleic acid encoding a multispecific CD4/CD8 antibody provided herein. Also provided is a vector comprising a nucleic acid encoding a multispecific CD4/CD8 antibody provided herein. Also provided is a host cell comprising a vector comprising a nucleic acid encoding a multispecific CD4/CD8 antibody provided herein. Also provided is a kit comprising the vector comprising a nucleic acid encoding a multispecific CD4/CD8 antibody provided herein, and packaging for the same. Also provided is an isolated nucleic acid encoding a monoclonal antibody provided herein. Also provided is an isolated nucleic acid encoding an antigen binding fragment provided herein. Also provided is a nucleic acid encoding a multispecific antibody comprising: (a) a first binding domain that binds to CD8, and (b) a second binding domain that binds to a CD4, as provided herein. In certain embodiments, the multispecific CD4/CD8 antibody is a trispecific antibody. In certain embodiments, the multispecific CD4/CD8 antibody is a quadraspecific antibody.


It will be appreciated by those skilled in the art that the coding sequence of a protein can be changed (e.g., replaced, deleted, inserted, etc.) without changing the amino acid sequence of the protein. Accordingly, it will be understood by those skilled in the art that nucleic acid sequences encoding antibodies provided herein can be altered without changing the amino acid sequences of the proteins.


Any vector known to those skilled in the art in view of the present disclosure can be used, such as a plasmid, a cosmid, a phage vector or a viral vector. In some embodiments, the vector is a recombinant expression vector such as a plasmid. The vector can include any element to establish a conventional function of an expression vector, for example, a promoter, ribosome binding element, terminator, enhancer, selection marker, and origin of replication. The promoter can be a constitutive, inducible or repressible promoter. A number of expression vectors capable of delivering nucleic acids to a cell are known in the art and can be used herein for production of an antibody or antigen-binding fragment thereof in the cell. Conventional cloning techniques or artificial gene synthesis can be used to generate a recombinant expression vector according to certain embodiments. Such techniques are well known to those skilled in the art in view of the present disclosure.


Also provided is a host cell comprising an isolated nucleic acid encoding an antibody provided herein. Also provided is a host cell comprising an isolated nucleic acid encoding an antigen binding fragment provided herein. Any host cell known to those skilled in the art in view of the present disclosure can be used for recombinant expression of antibodies or antigen-binding fragments thereof provided herein. In some embodiments, the host cells are E. coli TG1 or BL21 cells (for expression of, e.g., an scFv or Fab antibody), CHO-DG44 or CHO-K1 cells or HEK293 cells (for expression of, e.g., a full-length IgG antibody). According to particular embodiments, the recombinant expression vector is transformed into host cells by conventional methods such as chemical transfection, heat shock, or electroporation, where it is stably integrated into the host cell genome such that the recombinant nucleic acid is effectively expressed.


Also provided are methods of producing an antibody disclosed herein. The methods comprise culturing a cell comprising a nucleic acid encoding the antibody under conditions to produce an antibody and recovering the antibody from the cell or cell culture (e.g., from the supernatant). Expressed antibodies can be harvested from the cells and purified according to conventional techniques known in the art and as described herein.


Also provided is a method of producing a multispecific antibody disclosed herein. The methods comprise culturing a cell comprising a nucleic acid encoding the multispecific antibody thereof under conditions to produce the multispecific antibody and recovering the multispecific antibody from the cell or cell culture (e.g., from the supernatant). Expressed multispecific antibodies thereof can be harvested from the cells and purified according to conventional techniques known in the art and as described herein.


Pharmaceutical Compositions


In another general aspect, provided is a pharmaceutical composition comprising a CD8 antibody provided herein and a pharmaceutically acceptable carrier. In another general aspect, provided is a pharmaceutical composition comprising a CD4 antibody provided herein and a pharmaceutically acceptable carrier. In certain embodiments, the antibody is isolated. Also provided is a method of producing the pharmaceutical composition, comprising combining the antibody with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition.


In another general aspect, provided is a pharmaceutical composition comprising a CD8 multispecific antibody provided herein and a pharmaceutically acceptable carrier. In certain embodiments, the multispecific antibody is isolated. Also provided is a method of producing the pharmaceutical composition, comprising combining the multispecific antibody with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition. In another aspect, provided herein is a pharmaceutical composition comprising a comprising: (a) a first binding domain that binds to CD8, and (b) a second binding domain that binds to a second target that is not CD8, and a pharmaceutically acceptable carrier. Any of the multispecific antibodies provided herein are contemplated in the pharmaceutical compositions. In certain embodiments, the second binding domain binds to CD4.


In another general aspect, provided is a pharmaceutical composition comprising a CD4 multispecific antibody provided herein and a pharmaceutically acceptable carrier. In certain embodiments, the multispecific antibody is isolated. Also provided is a method of producing the pharmaceutical composition, comprising combining the multispecific antibody with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition. In another aspect, provided herein is a pharmaceutical composition comprising a comprising: (a) a first binding domain that binds to CD4, and (b) a second binding domain that binds to a second target that is not CD4, and a pharmaceutically acceptable carrier. Any of the multispecific antibodies provided herein are contemplated in the pharmaceutical compositions. In certain embodiments, the second binding domain binds to CD8.


In another general aspect, provided is a pharmaceutical composition comprising a multispecific CD4/CD8 antibody provided herein and a pharmaceutically acceptable carrier. In certain embodiments, the multispecific CD4/CD8 antibody is isolated. Also provided is a method of producing the pharmaceutical composition, comprising combining the multispecific antibody with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition. In another aspect, provided herein is a pharmaceutical composition comprising a comprising: (a) a first binding domain that binds to CD8, and (b) a second binding domain that binds to CD4, and a pharmaceutically acceptable carrier. Any of the multispecific antibodies provided herein are contemplated in the pharmaceutical compositions.


The term “pharmaceutical composition” as used herein means a product comprising an antibody provided herein together with a pharmaceutically acceptable carrier. Antibodies of provided herein and compositions comprising them are also useful in the manufacture of a medicament for therapeutic applications.


As used herein, the term “carrier” refers to any excipient, diluent, filler, salt, buffer, stabilizer, solubilizer, oil, lipid, lipid containing vesicle, microsphere, liposomal encapsulation, or other material well known in the art for use in pharmaceutical formulations. It will be understood that the characteristics of the carrier, excipient or diluent will depend on the route of administration for a particular application. As used herein, the term “pharmaceutically acceptable carrier” refers to a non-toxic material that does not interfere with the effectiveness of a composition provided herein the biological activity of a composition provided herein. According to particular embodiments, in view of the present disclosure, any pharmaceutically acceptable carrier suitable for use in an antibody pharmaceutical composition can be used herein.


The formulation of pharmaceutically active ingredients with pharmaceutically acceptable carriers is known in the art, e.g., Remington: The Science and Practice of Pharmacy (e.g. 21st edition (2005), and any later editions). Non-limiting examples of additional ingredients include: buffers, diluents, solvents, tonicity regulating agents, preservatives, stabilizers, and chelating agents. One or more pharmaceutically acceptable carriers can be used in formulating the pharmaceutical compositions provided herein.


In one embodiment, the pharmaceutical composition is a liquid formulation. A preferred example of a liquid formulation is an aqueous formulation, i.e., a formulation comprising water. The liquid formulation can comprise a solution, a suspension, an emulsion, a microemulsion, a gel, and the like. An aqueous formulation typically comprises at least 50% w/w water, or at least 60%, 70%, 75%, 80%, 85%, 90%, or at least 95% w/w of water.


In one embodiment, the pharmaceutical composition can be formulated as an injectable which can be injected, for example, via an injection device (e.g., a syringe or an infusion pump). The injection can be delivered subcutaneously, intramuscularly, intraperitoneally, intravitreally, or intravenously, for example.


In another embodiment, the pharmaceutical composition is a solid formulation, e.g., a freeze-dried or spray-dried composition, which can be used as is, or whereto the physician or the patient adds solvents, and/or diluents prior to use. Solid dosage forms can include tablets, such as compressed tablets, and/or coated tablets, and capsules (e.g., hard or soft gelatin capsules). The pharmaceutical composition can also be in the form of sachets, dragees, powders, granules, lozenges, or powders for reconstitution, for example.


The dosage forms can be immediate release, in which case they can comprise a water-soluble or dispersible carrier, or they can be delayed release, sustained release, or modified release, in which case they can comprise water-insoluble polymers that regulate the rate of dissolution of the dosage form in the gastrointestinal tract or under the skin.


In other embodiments, the pharmaceutical composition can be delivered intranasally, intrabuccally, or sublingually.


The pH in an aqueous formulation can be between pH 3 and pH 10. In one embodiment, the pH of the formulation is from about 7.0 to about 9.5. In another embodiment, the pH of the formulation is from about 3.0 to about 7.0.


In another embodiment, the pharmaceutical composition comprises a buffer. Non-limiting examples of buffers include: arginine, aspartic acid, bicine, citrate, disodium hydrogen phosphate, fumaric acid, glycine, glycylglycine, histidine, lysine, maleic acid, malic acid, sodium acetate, sodium carbonate, sodium dihydrogen phosphate, sodium phosphate, succinate, tartaric acid, tricine, and tris(hydroxymethyl)-aminomethane, and mixtures thereof. The buffer can be present individually or in the aggregate, in a concentration from about 0.01 mg/ml to about 50 mg/ml, for example from about 0.1 mg/ml to about 20 mg/ml. Pharmaceutical compositions comprising each one of these specific buffers constitute alternative embodiments.


In another embodiment, the pharmaceutical composition comprises a preservative. Non-limiting examples of preservatives include: benzethonium chloride, benzoic acid, benzyl alcohol, bronopol, butyl 4-hydroxybenzoate, chlorobutanol, chlorocresol, chlorohexidine, chlorphenesin, o-cresol, m-cresol, p-cresol, ethyl 4-hydroxybenzoate, imidurea, methyl 4-hydroxybenzoate, phenol, 2-phenoxyethanol, 2-phenylethanol, propyl 4-hydroxybenzoate, sodium dehydroacetate, thiomerosal, and mixtures thereof. The preservative can be present individually or in the aggregate, in a concentration from about 0.01 mg/ml to about 50 mg/ml, for example from about 0.1 mg/ml to about 20 mg/ml. Pharmaceutical compositions comprising each one of these specific preservatives constitute alternative embodiments.


In another embodiment, the pharmaceutical composition comprises an isotonic agent. Non-limiting examples of isotonic agents include a salt (such as sodium chloride), an amino acid (such as glycine, histidine, arginine, lysine, isoleucine, aspartic acid, tryptophan, and threonine), an alditol (such as glycerol, 1,2-propanediol propyleneglycol), 1,3-propanediol, and 1,3-butanediol), polyethyleneglycol (e.g. PEG400), and mixtures thereof. Another example of an isotonic agent includes a sugar. Non-limiting examples of sugars can include mono-, di-, or polysaccharides, or water-soluble glucans, including for example fructose, glucose, mannose, sorbose, xylose, maltose, lactose, sucrose, trehalose, dextran, pullulan, dextrin, cyclodextrin, alpha and beta-HPCD, soluble starch, hydroxyethyl starch, and sodium carboxymethyl-cellulose. Another example of an isotonic agent is a sugar alcohol, wherein the term “sugar alcohol” is defined as a C(4-8) hydrocarbon having at least one —OH group. Non-limiting examples of sugar alcohols include mannitol, sorbitol, inositol, galactitol, dulcitol, xylitol, and arabitol. The isotonic agent can be present individually or in the aggregate, in a concentration from about 0.01 mg/ml to about 50 mg/ml, for example from about 0.1 mg/ml to about 20 mg/ml. Pharmaceutical compositions comprising each one of these specific isotonic agents constitute alternative embodiments.


In another embodiment, the pharmaceutical composition comprises a chelating agent. Non-limiting examples of chelating agents include citric acid, aspartic acid, salts of ethylenediaminetetraacetic acid (EDTA), and mixtures thereof. The chelating agent can be present individually or in the aggregate, in a concentration from about 0.01 mg/ml to about 50 mg/ml, for example from about 0.1 mg/ml to about 20 mg/ml. Pharmaceutical compositions comprising each one of these specific chelating agents constitute alternative embodiments.


In another embodiment, the pharmaceutical composition comprises a stabilizer. Non-limiting examples of stabilizers include one or more aggregation inhibitors, one or more oxidation inhibitors, one or more surfactants, and/or one or more protease inhibitors.


In another embodiment, the pharmaceutical composition comprises a stabilizer, wherein said stabilizer is carboxy-/hydroxycellulose and derivates thereof (such as HPC, HPC-SL, HPC-L and HPMC), cyclodextrins, 2-methylthioethanol, polyethylene glycol (such as PEG 3350), polyvinyl alcohol (PVA), polyvinyl pyrrolidone, salts (such as sodium chloride), sulphur-containing substances such as monothioglycerol), or thioglycolic acid. The stabilizer can be present individually or in the aggregate, in a concentration from about 0.01 mg/ml to about 50 mg/ml, for example from about 0.1 mg/ml to about 20 mg/ml. Pharmaceutical compositions comprising each one of these specific stabilizers constitute alternative embodiments.


In further embodiments, the pharmaceutical composition comprises one or more surfactants, preferably a surfactant, at least one surfactant, or two different surfactants. The term “surfactant” refers to any molecules or ions that are comprised of a water-soluble (hydrophilic) part, and a fat-soluble (lipophilic) part. The surfactant can, for example, be selected from the group consisting of anionic surfactants, cationic surfactants, nonionic surfactants, and/or zwitterionic surfactants. The surfactant can be present individually or in the aggregate, in a concentration from about 0.1 mg/ml to about 20 mg/ml. Pharmaceutical compositions comprising each one of these specific surfactants constitute alternative embodiments.


In a further embodiment, the pharmaceutical composition comprises one or more protease inhibitors, such as, e.g., EDTA, and/or benzamidine hydrochloric acid (HCl). The protease inhibitor can be present individually or in the aggregate, in a concentration from about 0.1 mg/ml to about 20 mg/ml. Pharmaceutical compositions comprising each one of these specific protease inhibitors constitute alternative embodiments.


In another general aspect, provided herein is a method of producing a pharmaceutical composition comprising an antibody or antigen-binding fragment thereof provided herein, comprising combining an antibody or antigen-binding fragment thereof with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition.


Methods of Use


The functional activity of antibodies provided herein can be characterized by methods known in the art and as described herein. Methods for characterizing antibodies and antigen-binding fragments thereof include, but are not limited to, affinity and specificity assays including Biacore, ELISA, and OctetRed analysis; binding assays to detect the binding of antibodies to target cells by FACS; binding assays to detect the binding of antibodies to the target antigen on cells. According to particular embodiments, the methods for characterizing antibodies and antigen-binding fragments thereof include those described below. In certain embodiments, the antibody is a CD8 antibody. In certain embodiments, the antibody is a CD4 antibody. In certain embodiments, the antibody is a multispecific CD8 antibody. In certain embodiments, the antibody is a multispecific CD4 antibody. In certain embodiments, the antibody is a multispecific CD4/CD8 antibody.


Also provided is a method of activating a T cell expressing CD8, comprising contacting the T cell with a CD8 antibody provided herein. In some embodiments, the contacting results in an increase in CD69, CD25, and/or Granzyme B expression, as compared to a control T cell expressing CD8.


In another general aspect, provided is a method of inactivating a T cell expressing CD8, comprising contacting the T cell with an antibody that binds to a CD8 provided herein. In another general aspect, provided is a method of blocking activation of a T cell expressing CD8, comprising contacting the T cell with an antibody that binds to a CD8 provided herein. In another general aspect, provided is a method of modulating the activation of a T cell expressing CD8, comprising contacting the T cell with an antibody that binds to a CD8 provided herein.


Also provided herein is a method of activating a T cell expressing CD4, comprising contacting the T cell with a CD4 antibody, as provided herein. In some embodiments, the contacting results in an increase in CD69, CD25, and/or Granzyme B expression, as compared to a control T cell expressing CD4.


In another general aspect, provided is a method of inactivating a T cell expressing CD4, comprising contacting the T cell with an antibody that binds to a CD4 provided herein. In another general aspect, provided is a method of blocking activation of a T cell expressing CD4, comprising contacting the T cell with an antibody that binds to a CD4 provided herein. In another general aspect, provided is a method of modulating the activation of a T cell expressing CD4, comprising contacting the T cell with an antibody that binds to a CD4 provided herein.


Also provided herein is a method of treating a disease or disorder in a subject, comprising administering to the subject a CD8 antibody provided herein. Also provided herein is a method of treating a disease or disorder in a subject, comprising administering to the subject a CD8 antigen binding fragment provided herein. Also provided herein is a method of treating a disease or disorder in a subject, comprising administering to the subject a pharmaceutical composition comprising a CD8 antibody provided herein. Also provided herein is a method of treating a disease or disorder in a subject, comprising administering to the subject a pharmaceutical composition comprising a CD8 antigen binding fragment provided herein.


Also provided herein is a method of treating a disease or disorder in a subject, comprising administering to the subject a CD4 antibody provided herein. Also provided herein is a method of treating a disease or disorder in a subject, comprising administering to the subject a CD4 antigen binding fragment provided herein. Also provided herein is a method of treating a disease or disorder in a subject, comprising administering to the subject a pharmaceutical composition comprising a CD4 antibody provided herein. Also provided herein is a method of treating a disease or disorder in a subject, comprising administering to the subject a pharmaceutical composition comprising a CD4 antigen binding fragment provided herein.


Also provided herein is a method of activating a T cell expressing CD8, comprising contacting the T cell with the multispecific antibody, as provided herein. In some embodiments, the contacting results in an increase in CD69, CD25, and/or Granzyme B expression, as compared to a control T cell expressing CD8. In certain embodiments, the antibody is a multispecific CD4/CD8 antibody.


In another aspect, provided herein is a method of inactivating a T cell expressing CD8, comprising contacting the T cell with the multispecific antibody, as provided herein. In another aspect, provided herein is a method of blocking activation of a T cell expressing CD8, comprising contacting the T cell with the multispecific antibody, as provided herein. In another aspect, provided herein is a method of modulating the activation of a T cell expressing CD8, comprising contacting the T cell with the multispecific antibody, as provided herein. In certain embodiments, the antibody is a multispecific CD4/CD8 antibody.


Also provided herein is a method of activating a T cell expressing CD4, comprising contacting the T cell with the multispecific antibody, as provided herein. In some embodiments, the contacting results in an increase in CD69, CD25, and/or Granzyme B expression, as compared to a control T cell expressing CD4. In certain embodiments, the antibody is a multispecific CD4/CD8 antibody.


In another aspect, provided herein is a method of inactivating a T cell expressing CD4, comprising contacting the T cell with the multispecific antibody, as provided herein. In another aspect, provided herein is a method of blocking activation of a T cell expressing CD4, comprising contacting the T cell with the multispecific antibody, as provided herein. In another aspect, provided herein is a method of modulating the activation of a T cell expressing CD4, comprising contacting the T cell with the multispecific antibody, as provided herein. In certain embodiments, the antibody is a multispecific CD4/CD8 antibody.


In another aspect, provided herein is a method of directing a T cell expressing CD8 to a target cell, the method comprising contacting the T cell with a multispecific antibody provided herein. In some embodiments, the contacting directs the T cell to the target cell. Also provided is a method of targeting an antigen on the surface of a target cell, the method comprising exposing the target cell to a CD8 multispecific antibody or antigen binding fragment thereof provided herein. Also provided is a method of targeting an antigen on the surface of a target cell, the method comprising exposing the target cell to a pharmaceutical composition comprising a CD8 multispecific antibody or antigen binding fragment thereof provided herein. In certain embodiments, the antibody is a multispecific CD4/CD8 antibody.


In another general aspect, provided is a method of targeting an antigen on the surface of a target cell, the method comprising exposing the target cell to a CD8 multispecific antibody or antigen binding fragment thereof or a pharmaceutical composition provided herein. In certain embodiments, the antibody is a multispecific CD4/CD8 antibody.


Also provided is a method of directing CD8-expressing T cells to a second target. The methods can comprise contacting the CD8-expressing T cell with a CD8 multispecific antibody or antigen binding fragment thereof provided herein, wherein the CD8 multispecific antibody or antigen binding fragment thereof directs the CD8-expressing T cell to the second target. Also provided is a method of directing a T cell expressing CD8 to a second target, the method comprising contacting the T cell with a multispecific antibody provided herein, wherein the contacting directs the T cell to the second target. In certain embodiments, the antibody is a multispecific CD4/CD8 antibody.


Also provided is a method for inhibiting growth or proliferation of target cells. The methods can comprise contacting the CD8-expressing T cells with a CD8 multispecific antibody or antigen binding fragment thereof provided herein, wherein contacting the target cells with the CD8 multispecific antibody or antigen binding fragment thereof composition inhibits the growth or proliferation of the target cells. Also provided is a method of inhibiting growth or proliferation of target cells expressing a second target antigen on the cell surface, the method comprising contacting the target cells with a multispecific antibody provided herein, wherein contacting the target cells with the pharmaceutical composition inhibits growth or proliferation of the target cells. In some embodiments, the target cells are in the presence of a T cell expressing CD8 while in contact with the multispecific antibody. In certain embodiments, the antibody is a multispecific CD4/CD8 antibody.


In another aspect, provided herein is a method of directing a T cell expressing CD4 to a target cell, the method comprising contacting the T cell with a multispecific antibody provided herein. In some embodiments, the contacting directs the T cell to the target cell. Also provided is a method of targeting an antigen on the surface of a target cell, the method comprising exposing the target cell to a CD4 multispecific antibody or antigen binding fragment thereof provided herein. Also provided is a method of targeting an antigen on the surface of a target cell, the method comprising exposing the target cell to a pharmaceutical composition comprising a CD4 multispecific antibody or antigen binding fragment thereof provided herein. In certain embodiments, the antibody is a multispecific CD4/CD8 antibody.


In another general aspect, provided is a method of targeting an antigen on the surface of a target cell, the method comprising exposing the target cell to a CD4 multispecific antibody or antigen binding fragment thereof or a pharmaceutical composition provided herein. In certain embodiments, the antibody is a multispecific CD4/CD8 antibody.


Also provided is a method of directing CD4-expressing T cells to a second target. The methods can comprise contacting the CD4-expressing T cell with a CD4 multispecific antibody or antigen binding fragment thereof provided herein, wherein the CD4 multispecific antibody or antigen binding fragment thereof directs the CD4-expressing T cell to the second target. Also provided is a method of directing a T cell expressing CD4 to a second target, the method comprising contacting the T cell with a multispecific antibody provided herein, wherein the contacting directs the T cell to the second target. In certain embodiments, the antibody is a multispecific CD4/CD8 antibody.


Also provided is a method for inhibiting growth or proliferation of target cells. The methods can comprise contacting the CD4-expressing T cells with a CD4 multispecific antibody or antigen binding fragment thereof provided herein, wherein contacting the target cells with the CD4 multispecific antibody or antigen binding fragment thereof composition inhibits the growth or proliferation of the target cells. Also provided is a method of inhibiting growth or proliferation of target cells expressing a second target antigen on the cell surface, the method comprising contacting the target cells with a multispecific antibody provided herein, wherein contacting the target cells with the pharmaceutical composition inhibits growth or proliferation of the target cells. In some embodiments, the target cells are in the presence of a T cell expressing CD4 while in contact with the multispecific antibody. In certain embodiments, the antibody is a multispecific CD4/CD8 antibody.


Also provided herein is a method of treating a disease or disorder in a subject, comprising administering to the subject a CD8 multispecific antibody provided herein. Also provided herein is a method of treating a disease or disorder in a subject, comprising administering to the subject a multispecific antibody comprising a CD8 antigen binding fragment provided herein. Also provided herein is a method of treating a disease or disorder in a subject, comprising administering to the subject a pharmaceutical composition comprising a CD8 multispecific antibody provided herein. Also provided herein is a method of treating a disease or disorder in a subject, comprising administering to the subject a pharmaceutical composition comprising a multispecific antibody comprising a CD8 antigen binding fragment provided herein. In certain embodiments, the antibody is a multispecific CD4/CD8 antibody.


In another general aspect, provided herein is a method of treating a disease or disorder in a subject, comprising administering to the subject an isolated multispecific antibody or antigen binding fragment thereof that specifically binds CD8 and a second target antigen presented on the surface of a target cell, or a pharmaceutical composition disclosed herein. In some embodiments, provided is a method for eliminating target cells expressing the second antigen or treating a disease caused all or in part by target cells expressing the second antigen in a subject, comprising administering an effective amount of a multispecific antibody provided herein to the subject. In certain embodiments, the antibody is a multispecific CD4/CD8 antibody.


Also provided herein is a method of treating a disease or disorder in a subject, comprising administering to the subject a CD4 multispecific antibody provided herein. Also provided herein is a method of treating a disease or disorder in a subject, comprising administering to the subject a multispecific antibody comprising a CD4 antigen binding fragment provided herein. Also provided herein is a method of treating a disease or disorder in a subject, comprising administering to the subject a pharmaceutical composition comprising a CD4 multispecific antibody provided herein. Also provided herein is a method of treating a disease or disorder in a subject, comprising administering to the subject a pharmaceutical composition comprising a multispecific antibody comprising a CD4 antigen binding fragment provided herein. In certain embodiments, the antibody is a multispecific CD4/CD8 antibody.


In another general aspect, provided herein is a method of treating a disease or disorder in a subject, comprising administering to the subject an isolated multispecific antibody or antigen binding fragment thereof that specifically binds CD4 and a second target antigen presented on the surface of a target cell, or a pharmaceutical composition disclosed herein. In some embodiments, provided is a method for eliminating target cells expressing the second antigen or treating a disease caused all or in part by target cells expressing the second antigen in a subject, comprising administering an effective amount of a multispecific antibody provided herein to the subject. In certain embodiments, the antibody is a multispecific CD4/CD8 antibody.


In some embodiments, the subject is a subject in need thereof. In some embodiments, the subject is a human. In specific embodiments, the subject is administered an effective amount.


As used herein, the term “effective amount” refers to an amount of an active ingredient or component that elicits the desired biological or medicinal response in a subject.


According to particular embodiments, an effective amount refers to the amount of therapy which is sufficient to achieve one, two, three, four, or more of the following effects: (i) reduce or ameliorate the severity of the disease, disorder or condition to be treated or a symptom associated therewith; (ii) reduce the duration of the disease, disorder or condition to be treated, or a symptom associated therewith; (iii) prevent the progression of the disease, disorder or condition to be treated, or a symptom associated therewith; (iv) cause regression of the disease, disorder or condition to be treated, or a symptom associated therewith; (v) prevent the development or onset of the disease, disorder or condition to be treated, or a symptom associated therewith; (vi) prevent the recurrence of the disease, disorder or condition to be treated, or a symptom associated therewith; (vii) reduce hospitalization of a subject having the disease, disorder or condition to be treated, or a symptom associated therewith; (viii) reduce hospitalization length of a subject having the disease, disorder or condition to be treated, or a symptom associated therewith; (ix) increase the survival of a subject with the disease, disorder or condition to be treated, or a symptom associated therewith; (xi) inhibit or reduce the disease, disorder or condition to be treated, or a symptom associated therewith in a subject; and/or (xii) enhance or improve the prophylactic or therapeutic effect(s) of another therapy.


The effective amount or dosage can vary according to various factors, such as the disease, disorder or condition to be treated, the means of administration, the target site, the physiological state of the subject (including, e.g., age, body weight, health), whether the subject is a human or an animal, other medications administered, and whether the treatment is prophylactic or therapeutic. Treatment dosages are optimally titrated to optimize safety and efficacy.


According to particular embodiments, the compositions described herein are formulated to be suitable for the intended route of administration to a subject. For example, the compositions described herein can be formulated to be suitable for intravenous, subcutaneous, or intramuscular administration.


As used herein, the terms “treat,” “treating,” and “treatment” are all intended to refer to an amelioration or reversal of at least one measurable physical parameter related to a cancer, which is not necessarily discernible in the subject, but can be discernible in the subject. The terms “treat,” “treating,” and “treatment,” can also refer to causing regression, preventing the progression, or at least slowing down the progression of the disease, disorder, or condition. In a particular embodiment, “treat,” “treating,” and “treatment” refer to an alleviation, prevention of the development or onset, or reduction in the duration of one or more symptoms associated with the disease, disorder, or condition, such as a tumor or more preferably a cancer. In a particular embodiment, “treat,” “treating,” and “treatment” refer to prevention of the recurrence of the disease, disorder, or condition. In a particular embodiment, “treat,” “treating,” and “treatment” refer to an increase in the survival of a subject having the disease, disorder, or condition. In a particular embodiment, “treat,” “treating,” and “treatment” refer to elimination of the disease, disorder, or condition in the subject.


In some embodiments, a CD8 antibody provided herein is used in combination with a supplemental therapy. In some embodiments, a CD4 antibody provided herein is used in combination with a supplemental therapy.


As used herein, the term “in combination,” in the context of the administration of two or more therapies to a subject, refers to the use of more than one therapy. The use of the term “in combination” does not restrict the order in which therapies are administered to a subject. For example, a first therapy (e.g., a composition described herein) can be administered prior to (e.g., 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 16 hours, 24 hours, 48 hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, or 12 weeks before), concomitantly with, or subsequent to (e.g., 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 16 hours, 24 hours, 48 hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, or 12 weeks after) the administration of a second therapy to a subject.


Enrichment and Detection Methods


In one aspect, the CD8 antibodies provided herein are used as agents to detect CD8-expressing cells. Thus, in other methods, provided is a method of detecting a cell expressing CD8, comprising contacting a cell with a CD8 antibody provided herein. In certain embodiments, the detecting is by ELISA. In some embodiments, the detecting is by FACS analysis. Also provided are kits comprising a CD8 antibody provided herein, and instructions for use.


Enrichment, isolation, separation, purification, sorting, selecting, capturing or detecting, or any combination thereof can be done using known technologies such as bead, microfluidics, solid support, columns, and the like. For example, CD8+ CTL may be separated or visualized using known methods when bound to the CD8 antibodies provided herein.


The CD8 antibodies or multispecific CD8 antibodies provided herein can be used to selectively enrich, isolate, separate, purify, sort, select, capture or detect CD8-expressing cells. The CD8 antibodies or multispecific CD8 antibodies provided herein may be utilized in a bispecific format, e.g. containing a first antigen binding domain that specifically binds CD8 and a second antigen binding domain that specifically binds a second target. In other embodiments, the multispecific CD8 antibodies provided herein may be utilized in a format that further incorporates a third antigen binding domain that specifically binds a third antigen (e.g., at a trispecific antibody). In other embodiments, the multispecific CD8 antibodies provided herein may be utilized in a format that further incorporates a fourth antigen binding domain that specifically binds a fourth antigen. (e.g., as a quadraspecific antibody).


In one aspect, provided herein is a method of enriching a CD8-expressing cell comprising: providing a sample comprising the CD8-expressing cell; contacting the sample with a CD8 antibody provided herein; and enriching the CD8-expressing cell bound to the CD8 antibody. In one aspect, provided herein is a method of isolating a CD8-expressing cell comprising: providing a sample comprising the CD8-expressing cell; contacting the sample with a CD8 antibody provided herein; and isolating the CD8-expressing cell bound to the CD8 antibody. In one aspect, provided herein is a method of separating a CD8-expressing cell comprising: providing a sample comprising the CD8-expressing cell; contacting the sample with a CD8 antibody provided herein; and separating the CD8-expressing cell bound to the CD8 antibody. In one aspect, provided herein is a method of purifying a CD8-expressing cell comprising: providing a sample comprising the CD8-expressing cell; contacting the sample with a CD8 antibody provided herein; and purifying the CD8-expressing cell bound to the CD8 antibody. In one aspect, provided herein is a method of sorting a CD8-expressing cell comprising: providing a sample comprising the CD8-expressing cell; contacting the sample with a CD8 antibody provided herein; and sorting the CD8-expressing cell bound to the CD8 antibody. In one aspect, provided herein is a method of selecting a CD8-expressing cell comprising: providing a sample comprising the CD8-expressing cell; contacting the sample with a CD8 antibody provided herein; and selecting the CD8-expressing cell bound to the CD8 antibody. In one aspect, provided herein is a method of capturing a CD8-expressing cell comprising: providing a sample comprising the CD8-expressing cell; contacting the sample with a CD8 antibody provided herein; and capturing the CD8-expressing cell bound to the CD8 antibody. In one aspect, provided herein is a method of detecting a CD8-expressing cell comprising: providing a sample comprising the CD8-expressing cell; contacting the sample with a CD8 antibody provided herein; and detecting the CD8-expressing cell bound to the CD8 antibody.


In one aspect, provided herein is a method of enriching a CD8-expressing cell comprising: contacting a CD8-expressing cell with a CD8 antibody provided herein; and enriching the CD8-expressing cell bound to the CD8 antibody. In one aspect, provided herein is a method of isolating a CD8-expressing cell comprising: contacting a CD8-expressing cell with a CD8 antibody provided herein; and isolating the CD8-expressing cell bound to the CD8 antibody. In one aspect, provided herein is a method of separating a CD8-expressing cell comprising: contacting a CD8-expressing cell with a CD8 antibody provided herein; and separating the CD8-expressing cell bound to the CD8 antibody. In one aspect, provided herein is a method of purifying a CD8-expressing cell comprising: contacting a CD8-expressing cell with a CD8 antibody provided herein; and purifying the CD8-expressing cell bound to the CD8 antibody. In one aspect, provided herein is a method of sorting a CD8-expressing cell comprising: contacting a CD8-expressing cell with a CD8 antibody provided herein; and sorting the CD8-expressing cell bound to the CD8 antibody. In one aspect, provided herein is a method of selecting a CD8-expressing cell comprising: contacting a CD8-expressing cell with a CD8 antibody provided herein; and selecting the CD8-expressing cell bound to the CD8 antibody. In one aspect, provided herein is a method of capturing a CD8-expressing cell comprising: contacting a CD8-expressing cell with a CD8 antibody provided herein; and capturing the CD8-expressing cell bound to the CD8 antibody. In one aspect, provided herein is a method of detecting a CD8-expressing cell comprising: contacting a CD8-expressing cell with a CD8 antibody provided herein; and detecting the CD8-expressing cell bound to the CD8 antibody.


In one aspect, provided herein is a method of enriching a CD8-expressing cell comprising: contacting a CD8-expressing cell with a CD8 antibody provided herein; and enriching the CD8-expressing cell based on binding of the CD8-expressing cell to the CD8 antibody. In one aspect, provided herein is a method of isolating a CD8-expressing cell comprising: contacting a CD8-expressing cell with a CD8 antibody provided herein; and isolating the CD8-expressing cell based on binding of the CD8-expressing cell to the CD8 antibody. In one aspect, provided herein is a method of separating a CD8-expressing cell comprising: contacting a CD8-expressing cell with a CD8 antibody provided herein; and separating the CD8-expressing cell based on binding of the CD8-expressing cell to the CD8 antibody. In one aspect, provided herein is a method of purifying a CD8-expressing cell comprising: contacting a CD8-expressing cell with a CD8 antibody provided herein; and purifying the CD8-expressing cell based on binding of the CD8-expressing cell to the CD8 antibody. In one aspect, provided herein is a method of sorting a CD8-expressing cell comprising: contacting a CD8-expressing cell with a CD8 antibody provided herein; and sorting the CD8-expressing cell based on binding of the CD8-expressing cell to the CD8 antibody. In one aspect, provided herein is a method of selecting a CD8-expressing cell comprising: contacting a CD8-expressing cell with a CD8 antibody provided herein; and selecting the CD8-expressing cell based on binding of the CD8-expressing cell to the CD8 antibody. In one aspect, provided herein is a method of capturing a CD8-expressing cell comprising: contacting a CD8-expressing cell with a CD8 antibody provided herein; and capturing the CD8-expressing cell based on binding of the CD8-expressing cell to the CD8 antibody. In one aspect, provided herein is a method of detecting a CD8-expressing cell comprising: contacting a CD8-expressing cell with a CD8 antibody provided herein; and detecting the CD8-expressing cell based on binding of the CD8-expressing cell to the CD8 antibody.


In certain embodiments of the methods, the CD8-expressing cell is a T cell. In certain embodiments of the methods, the CD8-expressing cell is a CD8+ cytotoxic T lymphocyte (CTL). In some embodiments of the methods, the CD8-expressing cell is in a population of cells. In some embodiments of the methods, the CD8-expressing cell is in a population of lymphocytes. In some embodiments of the methods, the CD8-expressing cell is in a population of T cells. In some embodiments of the methods, the CD8-expressing cell is provided as a population of cells. In some embodiments of the methods, the CD8-expressing cell is provided as a population of lymphocytes. In some embodiments of the methods, the CD8-expressing cell is provided as a population of T cells. In some embodiments of the methods, the CD8-expressing cell is provided as a sample comprising a population of cells. In some embodiments of the methods, the CD8-expressing cell is provided as a sample comprising a population of lymphocytes. In some embodiments of the methods, the CD8-expressing cell is provided as a sample comprising a population of T cells. In some embodiments of the methods, the sample is a blood sample. In some embodiments of the methods, the sample is a tissue sample. In some embodiments of the methods, the sample is a tissue culture sample.


In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody provided herein. In some embodiments of the methods, the CD8 antibody is a bispecific CD8 antibody provided herein. In some embodiments of the methods, the CD8 antibody is a trispecific CD8 antibody provided herein. In some embodiments of the methods, the CD8 antibody is a quadraspecific CD8 antibody provided herein. In certain embodiments, the CD8 antibody specifically binds to CD8. In one embodiment, the multispecific CD8 antibody comprises: (a) a first binding domain that binds CD8, and (b) a second binding domain that binds to a second target. In one embodiment, the multispecific CD8 antibody comprises: (a) a first binding domain that binds CD8, and (b) a second binding domain that binds to a second target, and (c) a third binding domain that binds to a third target. In one embodiment, the multispecific CD8 antibody comprises: (a) a first binding domain that binds CD8, and (b) a second binding domain that binds to a second target, (c) a third binding domain that binds to a third target, and (d) a fourth binding domain that binds to a fourth target. In one embodiment, the multispecific CD8 antibody comprises: (a) a first binding domain that specifically binds CD8, and (b) a second binding domain that specifically binds to a second target. In one embodiment, the multispecific CD8 antibody comprises: (a) a first binding domain that specifically binds CD8, and (b) a second binding domain that specifically binds to a second target, and (c) a third binding domain that specifically binds to a third target. In one embodiment, the multispecific CD8 antibody comprises: (a) a first binding domain that specifically binds CD8, and (b) a second binding domain that specifically binds to a second target, (c) a third binding domain that specifically binds to a third target, and (d) a fourth binding domain that specifically binds to a fourth target.


In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4. In some embodiments, the second target is a TCR complex. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD3. In some embodiments, CD3 comprises CD3ε. In some embodiments, CD3 comprises CD3γ. In some embodiments, CD3 comprises CD3δ. In some embodiments, CD3 comprises CD3ζ. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD3ε. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD3γ. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD3δ. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD3ζ. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is a TCRα chain. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is a TCRβ chain. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is a TCRγ chain. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is a TCRδ chain. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is a T cell costimulatory molecule. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD28. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CTLA4. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is ICOS. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is 4-1BB. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is GITR. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD27. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is OX40. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD40L. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is HVEM. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is Galectin-9. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is TIM-1 In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is LFA1 In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD2. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is PD1. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the third target is a TCR complex. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the third target is CD3. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the third target is CD3ε. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the third target is CD3γ. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the third target is CD3δ. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the third target is CD3ζ. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the third target is a TCRα chain. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the third target is a TCRβ chain. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the third target is a TCRγ chain. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the third target is a TCRδ chain. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the third target is a T cell costimulatory molecule. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the third target is CD28. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the third target is CTLA4. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the third target is ICOS. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the third target is 4-1BB. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the third target is GITR. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the third target is CD27. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the third target is OX40. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the third target is CD40L. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the third target is HVEM. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the third target is Galectin-9. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the third target is TIM-1 In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the third target is LFA1 In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the third target is CD2. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the third target is PD1. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the fourth target is a TCR complex. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the fourth target is CD3. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the fourth target is CD3ε. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the fourth target is CD3γ. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the fourth target is CD3δ. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the fourth target is CD3ζ. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the fourth target is a TCRα chain. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the fourth target is a TCRβ chain. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the fourth target is a TCRγ chain. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the fourth target is a TCRδ chain. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the fourth target is a T cell costimulatory molecule. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the fourth target is CD28. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the fourth target is CTLA4. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the fourth target is ICOS. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the fourth target is 4-1BB. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the fourth target is GITR. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the fourth target is CD27. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the fourth target is OX40. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the fourth target is CD40L. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the fourth target is HVEM. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the fourth target is Galectin-9. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the fourth target is TIM-1. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the fourth target is LFA1. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the fourth target is CD2. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the fourth target is PD1. In some embodiments, the second target is CD4. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the third target is CD3. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the third target is TCRα chain. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the third target is a TCRβ chain. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the third target is a TCRγ chain. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the third target is a TCRδ chain. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the third target is CD28. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the fourth target is CD28.


In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, and the third target is a TCR complex. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, and the third target is CD3. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, and the third target is CD3ε. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, and the third target is CD3γ. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, and the third target is CD3δ. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, and the third target is CD3ζ. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, and the third target is a TCRα chain. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, and the third target is a TCRβ chain. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, and the third target is a TCRγ chain.


In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, and the third target is a T cell costimulatory molecule. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, and the third target is CD28. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, and the third target is CTLA4. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, and the third target is ICOS. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, and the third target is 4-1BB. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, and the third target is GITR. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, and the third target is CD27. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, and the third target is OX40. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, and the third target is CD40L. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, and the third target is HVEM. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, and the third target is Galectin-9. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, and the third target is TIM-1. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, and the third target is LFA1. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, and the third target is CD2. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, and the third target is PD1.


In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, the third target is a TCR complex, and the fourth target is a T cell costimulatory molecule. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, the third target is CD3, and the fourth target is a T cell costimulatory molecule. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, the third target is CD3ε, and the fourth target is a T cell costimulatory molecule. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, the third target is CD3γ, and the fourth target is a T cell costimulatory molecule. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, the third target is CD3δ, and the fourth target is a T cell costimulatory molecule. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, the third target is CD3ζ, and the fourth target is a T cell costimulatory molecule. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, the third target is a TCRα chain, and the fourth target is a T cell costimulatory molecule. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, the third target is a TCRβ chain, and the fourth target is a T cell costimulatory molecule. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD4, the third target is a TCRγ chain, and the fourth target is a T cell costimulatory molecule. In certain embodiments, the T cell costimulatory molecule is CD28. In certain embodiments, the T cell costimulatory molecule is CTLA4. In certain embodiments, the T cell costimulatory molecule is ICOS. In certain embodiments, the T cell costimulatory molecule is 4-1BB. In certain embodiments, the T cell costimulatory molecule is GITR. In certain embodiments, the T cell costimulatory molecule is CD27. In certain embodiments, the T cell costimulatory molecule is OX40. In certain embodiments, the T cell costimulatory molecule is CD40L. In certain embodiments, the T cell costimulatory molecule is HVEM. In certain embodiments, the T cell costimulatory molecule is Galectin-9. In certain embodiments, the T cell costimulatory molecule is TIM-1. In certain embodiments, the T cell costimulatory molecule is LFA1. In certain embodiments, the T cell costimulatory molecule is CD2. In certain embodiments, the T cell costimulatory molecule is PD1.


In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is a TCR complex, and the third target is a T cell costimulatory molecule. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD3, and the third target is a T cell costimulatory molecule. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD3ε, and the third target is a T cell costimulatory molecule. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD3γ, and the third target is a T cell costimulatory molecule. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD3δ, and the third target is a T cell costimulatory molecule. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is CD3ζ, and the third target is a T cell costimulatory molecule. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is a TCRα chain, and the third target is a T cell costimulatory molecule. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is a TCRβ chain, and the third target is a T cell costimulatory molecule. In some embodiments of the methods, the CD8 antibody is a multispecific CD8 antibody, wherein the second target is a TCRγ chain, and the third target is a T cell costimulatory molecule. In certain embodiments, the T cell costimulatory molecule is CD28. In certain embodiments, the T cell costimulatory molecule is CTLA4. In certain embodiments, the T cell costimulatory molecule is ICOS. In certain embodiments, the T cell costimulatory molecule is 4-1BB. In certain embodiments, the T cell costimulatory molecule is GITR. In certain embodiments, the T cell costimulatory molecule is CD27. In certain embodiments, the T cell costimulatory molecule is OX40. In certain embodiments, the T cell costimulatory molecule is CD40L. In certain embodiments, the T cell costimulatory molecule is HVEM. In certain embodiments, the T cell costimulatory molecule is Galectin-9. In certain embodiments, the T cell costimulatory molecule is TIM-1. In certain embodiments, the T cell costimulatory molecule is LFA1. In certain embodiments, the T cell costimulatory molecule is CD2. In certain embodiments, the T cell costimulatory molecule is PD1.


In specific embodiments of the methods provided herein, the method uses multi-marker detection. In some embodiments, the multi-marker detection uses a multispecific CD8 antibody provided herein. In some embodiments, the multi-marker detection uses a bispecific CD8 antibody provided herein. In some embodiments, the multi-marker detection uses a trispecific CD8 antibody provided herein. In some embodiments, the multi-marker detection uses a quadraspecific CD8 antibody provided herein.


In certain embodiments of the methods provided herein, the methods are included as steps in a T cell manufacturing process. In certain embodiments, the cells are CAR-T cells. In certain embodiments of the methods provided herein, the methods are included as steps in a T cell modification process.


In certain embodiments of the methods provided herein, the methods are included as steps in a diagnostic method. In certain embodiments of the methods provided herein, the methods are included as steps in a method to quantify the CD8-expressing T cells.


In certain embodiments of the methods provided herein, the method further comprises expanding the enriched, isolated, separated, purified, sorted, selected, captured or detected CD8-expressing cells. In certain embodiments, the expanding is in vitro. In certain embodiments, the expanding is in vivo. In certain embodiments of the methods provided herein, the method further comprises growing the enriched, isolated, separated, purified, sorted, selected, captured or detected CD8-expressing cells. In certain embodiments, the growing is in vitro. In certain embodiments, the growing is in vivo. In certain embodiments of the methods provided herein, the method further comprises quantifying the enriched, isolated, separated, purified, sorted, selected, captured or detected CD8-expressing cells.


In another aspect, the CD4 antibodies provided herein are used as agents to detect CD4-expressing cells. Thus, in other methods, provided is a method of detecting a cell expressing CD4, comprising contacting a cell with a CD4 antibody provided herein. In certain embodiments, the detecting is by ELISA. In some embodiments, the detecting is by FACS analysis. Also provided are kits comprising a CD4 antibody provided herein, and instructions for use.


Enrichment, isolation, separation, purification, sorting, selecting, capturing or detecting, or any combination thereof can be done using known technologies such as bead, microfluidics, solid support, columns, and the like. For example, CD4+ T cells, such as T helper cells, may be separated or visualized using known methods when bound to the CD4 antibodies provided herein.


The CD4 antibodies or multispecific CD4 antibodies provided herein can be used to selectively enrich, isolate, separate, purify, sort, select, capture or detect CD4-expressing cells. The CD4 antibodies or multispecific CD4 antibodies provided herein may be utilized in a bispecific format, e.g. containing a first antigen binding domain that specifically binds CD4 and a second antigen binding domain that specifically binds a second target. In other embodiments, the multispecific CD4 antibodies provided herein may be utilized in a format that further incorporates a third antigen binding domain that specifically binds a third antigen (e.g., at a trispecific antibody). In other embodiments, the multispecific CD4 antibodies provided herein may be utilized in a format that further incorporates a fourth antigen binding domain that specifically binds a fourth antigen. (e.g., as a quadraspecific antibody).


In one aspect, provided herein is a method of enriching a CD4-expressing cell comprising: providing a sample comprising the CD4-expressing cell; contacting the sample with a CD4 antibody provided herein; and enriching the CD4-expressing cell bound to the CD4 antibody. In one aspect, provided herein is a method of isolating a CD4-expressing cell comprising: providing a sample comprising the CD4-expressing cell; contacting the sample with a CD4 antibody provided herein; and isolating the CD4-expressing cell bound to the CD4 antibody. In one aspect, provided herein is a method of separating a CD4-expressing cell comprising: providing a sample comprising the CD4-expressing cell; contacting the sample with a CD4 antibody provided herein; and separating the CD4-expressing cell bound to the CD4 antibody. In one aspect, provided herein is a method of purifying a CD4-expressing cell comprising: providing a sample comprising the CD4-expressing cell; contacting the sample with a CD4 antibody provided herein; and purifying the CD4-expressing cell bound to the CD4 antibody. In one aspect, provided herein is a method of sorting a CD4-expressing cell comprising: providing a sample comprising the CD4-expressing cell; contacting the sample with a CD4 antibody provided herein; and sorting the CD4-expressing cell bound to the CD4 antibody. In one aspect, provided herein is a method of selecting a CD4-expressing cell comprising: providing a sample comprising the CD4-expressing cell; contacting the sample with a CD4 antibody provided herein; and selecting the CD4-expressing cell bound to the CD4 antibody. In one aspect, provided herein is a method of capturing a CD4-expressing cell comprising: providing a sample comprising the CD4-expressing cell; contacting the sample with a CD4 antibody provided herein; and capturing the CD4-expressing cell bound to the CD4 antibody. In one aspect, provided herein is a method of detecting a CD4-expressing cell comprising: providing a sample comprising the CD4-expressing cell; contacting the sample with a CD4 antibody provided herein; and detecting the CD4-expressing cell bound to the CD4 antibody.


In one aspect, provided herein is a method of enriching a CD4-expressing cell comprising: contacting a CD4-expressing cell with a CD4 antibody provided herein; and enriching the CD4-expressing cell bound to the CD4 antibody. In one aspect, provided herein is a method of isolating a CD4-expressing cell comprising: contacting a CD4-expressing cell with a CD4 antibody provided herein; and isolating the CD4-expressing cell bound to the CD4 antibody. In one aspect, provided herein is a method of separating a CD4-expressing cell comprising: contacting a CD4-expressing cell with a CD4 antibody provided herein; and separating the CD4-expressing cell bound to the CD4 antibody. In one aspect, provided herein is a method of purifying a CD4-expressing cell comprising: contacting a CD4-expressing cell with a CD4 antibody provided herein; and purifying the CD4-expressing cell bound to the CD4 antibody. In one aspect, provided herein is a method of sorting a CD4-expressing cell comprising: contacting a CD4-expressing cell with a CD4 antibody provided herein; and sorting the CD4-expressing cell bound to the CD4 antibody. In one aspect, provided herein is a method of selecting a CD4-expressing cell comprising: contacting a CD4-expressing cell with a CD4 antibody provided herein; and selecting the CD4-expressing cell bound to the CD4 antibody. In one aspect, provided herein is a method of capturing a CD4-expressing cell comprising: contacting a CD4-expressing cell with a CD4 antibody provided herein; and capturing the CD4-expressing cell bound to the CD4 antibody. In one aspect, provided herein is a method of detecting a CD4-expressing cell comprising: contacting a CD4-expressing cell with a CD4 antibody provided herein; and detecting the CD4-expressing cell bound to the CD4 antibody.


In one aspect, provided herein is a method of enriching a CD4-expressing cell comprising: contacting a CD4-expressing cell with a CD4 antibody provided herein; and enriching the CD4-expressing cell based on binding of the CD4-expressing cell to the CD4 antibody. In one aspect, provided herein is a method of isolating a CD4-expressing cell comprising: contacting a CD4-expressing cell with a CD4 antibody provided herein; and isolating the CD4-expressing cell based on binding of the CD4-expressing cell to the CD4 antibody. In one aspect, provided herein is a method of separating a CD4-expressing cell comprising: contacting a CD4-expressing cell with a CD4 antibody provided herein; and separating the CD4-expressing cell based on binding of the CD4-expressing cell to the CD4 antibody. In one aspect, provided herein is a method of purifying a CD4-expressing cell comprising: contacting a CD4-expressing cell with a CD4 antibody provided herein; and purifying the CD4-expressing cell based on binding of the CD4-expressing cell to the CD4 antibody. In one aspect, provided herein is a method of sorting a CD4-expressing cell comprising: contacting a CD4-expressing cell with a CD4 antibody provided herein; and sorting the CD4-expressing cell based on binding of the CD4-expressing cell to the CD4 antibody. In one aspect, provided herein is a method of selecting a CD4-expressing cell comprising: contacting a CD4-expressing cell with a CD4 antibody provided herein; and selecting the CD4-expressing cell based on binding of the CD4-expressing cell to the CD4 antibody. In one aspect, provided herein is a method of capturing a CD4-expressing cell comprising: contacting a CD4-expressing cell with a CD4 antibody provided herein; and capturing the CD4-expressing cell based on binding of the CD4-expressing cell to the CD4 antibody. In one aspect, provided herein is a method of detecting a CD4-expressing cell comprising: contacting a CD4-expressing cell with a CD4 antibody provided herein; and detecting the CD4-expressing cell based on binding of the CD4-expressing cell to the CD4 antibody.


In certain embodiments of the methods, the CD4-expressing cell is a T cell. In certain embodiments of the methods, the CD4-expressing cell is a CD4+ T helper cell. In some embodiments of the methods, the CD4-expressing cell is in a population of cells. In some embodiments of the methods, the CD4-expressing cell is in a population of lymphocytes. In some embodiments of the methods, the CD4-expressing cell is in a population of T cells. In some embodiments of the methods, the CD4-expressing cell is provided as a population of cells. In some embodiments of the methods, the CD4-expressing cell is provided as a population of lymphocytes. In some embodiments of the methods, the CD4-expressing cell is provided as a population of T cells. In some embodiments of the methods, the CD4-expressing cell is provided as a sample comprising a population of cells. In some embodiments of the methods, the CD4-expressing cell is provided as a sample comprising a population of lymphocytes. In some embodiments of the methods, the CD4-expressing cell is provided as a sample comprising a population of T cells. In some embodiments of the methods, the sample is a blood sample. In some embodiments of the methods, the sample is a tissue sample. In some embodiments of the methods, the sample is a tissue culture sample.


In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody provided herein. In some embodiments of the methods, the CD4 antibody is a bispecific CD4 antibody provided herein. In some embodiments of the methods, the CD4 antibody is a trispecific CD4 antibody provided herein. In some embodiments of the methods, the CD4 antibody is a quadraspecific CD4 antibody provided herein. In certain embodiments, the CD4 antibody specifically binds to CD4. In one embodiment, the multispecific CD4 antibody comprises: (a) a first binding domain that binds CD4, and (b) a second binding domain that binds to a second target. In one embodiment, the multispecific CD4 antibody comprises: (a) a first binding domain that binds CD4, and (b) a second binding domain that binds to a second target, and (c) a third binding domain that binds to a third target. In one embodiment, the multispecific CD4 antibody comprises: (a) a first binding domain that binds CD4, and (b) a second binding domain that binds to a second target, (c) a third binding domain that binds to a third target, and (d) a fourth binding domain that binds to a fourth target. In one embodiment, the multispecific CD4 antibody comprises: (a) a first binding domain that specifically binds CD4, and (b) a second binding domain that specifically binds to a second target. In one embodiment, the multispecific CD4 antibody comprises: (a) a first binding domain that specifically binds CD4, and (b) a second binding domain that specifically binds to a second target, and (c) a third binding domain that specifically binds to a third target. In one embodiment, the multispecific CD4 antibody comprises: (a) a first binding domain that specifically binds CD4, and (b) a second binding domain that specifically binds to a second target, (c) a third binding domain that specifically binds to a third target, and (d) a fourth binding domain that specifically binds to a fourth target.


In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8. In some embodiments, the second target is a TCR complex. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD3. In some embodiments, CD3 comprises CD3ε. In some embodiments, CD3 comprises CD3γ. In some embodiments, CD3 comprises CD3δ. In some embodiments, CD3 comprises CD3ζ. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD3ε. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD3γ. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD3δ. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD3ζ. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is a TCRα chain. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is a TCRβ chain. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is a TCRγ chain. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is a TCRδ chain. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is a T cell costimulatory molecule. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD28. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CTLA4. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is ICOS. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is 4-1BB. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is GITR. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD27. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is OX40. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD40L. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is HVEM. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is Galectin-9. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is TIM-1. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is LFA1. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD2. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is PD1. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the third target is a TCR complex. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the third target is CD3. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the third target is CD3ε. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the third target is CD3γ. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the third target is CD3δ. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the third target is CD3ζ. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the third target is a TCRα chain. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the third target is a TCRβ chain. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the third target is a TCRγ chain. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the third target is a TCRδ chain. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the third target is a T cell costimulatory molecule. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the third target is CD28. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the third target is CTLA4. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the third target is ICOS. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the third target is 4-1BB. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the third target is GITR. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the third target is CD27. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the third target is OX40. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the third target is CD40L. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the third target is HVEM. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the third target is Galectin-9. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the third target is TIM-1. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the third target is LFA1. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the third target is CD2. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the third target is PD1. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the fourth target is a TCR complex. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the fourth target is CD3. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the fourth target is CD3ε. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the fourth target is CD3γ. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the fourth target is CD3δ. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the fourth target is CD3ζ. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the fourth target is a TCRα chain. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the fourth target is a TCRβ chain. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the fourth target is a TCRγ chain. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the fourth target is a TCRδ chain. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the fourth target is a T cell costimulatory molecule. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the fourth target is CD28. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the fourth target is CTLA4. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the fourth target is ICOS. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the fourth target is 4-1BB. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the fourth target is GITR. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the fourth target is CD27. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the fourth target is OX40. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the fourth target is CD40L. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the fourth target is HVEM. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the fourth target is Galectin-9. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the fourth target is TIM-1. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the fourth target is LFA1. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the fourth target is CD2. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the fourth target is PD1. In some embodiments, the second target is CD8. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the third target is CD3. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the third target is TCRα chain. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the third target is a TCRβ chain. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the third target is a TCRγ chain. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the third target is a TCRδ chain. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the third target is CD28. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the fourth target is CD28.


In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, and the third target is a TCR complex. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, and the third target is CD3. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, and the third target is CD3ε. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, and the third target is CD3γ. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, and the third target is CD3δ. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, and the third target is CD3ζ. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, and the third target is a TCRα chain. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, and the third target is a TCRβ chain. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, and the third target is a TCRγ chain.


In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, and the third target is a T cell costimulatory molecule. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, and the third target is CD28. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, and the third target is CTLA4. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, and the third target is ICOS. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, and the third target is 4-1BB. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, and the third target is GITR. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, and the third target is CD27. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, and the third target is OX40. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, and the third target is CD40L. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, and the third target is HVEM. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, and the third target is Galectin-9. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, and the third target is TIM-1. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, and the third target is LFA1. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, and the third target is CD2. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, and the third target is PD1.


In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, the third target is a TCR complex, and the fourth target is a T cell costimulatory molecule. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, the third target is CD3, and the fourth target is a T cell costimulatory molecule. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, the third target is CD3ε, and the fourth target is a T cell costimulatory molecule. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, the third target is CD3γ, and the fourth target is a T cell costimulatory molecule. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, the third target is CD3δ, and the fourth target is a T cell costimulatory molecule. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, the third target is CD3ζ, and the fourth target is a T cell costimulatory molecule. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, the third target is a TCRα chain, and the fourth target is a T cell costimulatory molecule. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, the third target is a TCRβ chain, and the fourth target is a T cell costimulatory molecule. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD8, the third target is a TCRγ chain, and the fourth target is a T cell costimulatory molecule. In certain embodiments, the T cell costimulatory molecule is CD28. In certain embodiments, the T cell costimulatory molecule is CTLA4. In certain embodiments, the T cell costimulatory molecule is ICOS. In certain embodiments, the T cell costimulatory molecule is 4-1BB. In certain embodiments, the T cell costimulatory molecule is GITR. In certain embodiments, the T cell costimulatory molecule is CD27. In certain embodiments, the T cell costimulatory molecule is OX40. In certain embodiments, the T cell costimulatory molecule is CD40L. In certain embodiments, the T cell costimulatory molecule is HVEM. In certain embodiments, the T cell costimulatory molecule is Galectin-9. In certain embodiments, the T cell costimulatory molecule is TIM-1. In certain embodiments, the T cell costimulatory molecule is LFA1. In certain embodiments, the T cell costimulatory molecule is CD2. In certain embodiments, the T cell costimulatory molecule is PD1.


In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is a TCR complex, and the third target is a T cell costimulatory molecule. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD3, and the third target is a T cell costimulatory molecule. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD3ε, and the third target is a T cell costimulatory molecule. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD3γ, and the third target is a T cell costimulatory molecule. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD3δ, and the third target is a T cell costimulatory molecule. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is CD3ζ, and the third target is a T cell costimulatory molecule. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is a TCRα chain, and the third target is a T cell costimulatory molecule. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is a TCRβ chain, and the third target is a T cell costimulatory molecule. In some embodiments of the methods, the CD4 antibody is a multispecific CD4 antibody, wherein the second target is a TCRγ chain, and the third target is a T cell costimulatory molecule. In certain embodiments, the T cell costimulatory molecule is CD28. In certain embodiments, the T cell costimulatory molecule is CTLA4. In certain embodiments, the T cell costimulatory molecule is ICOS. In certain embodiments, the T cell costimulatory molecule is 4-1BB. In certain embodiments, the T cell costimulatory molecule is GITR. In certain embodiments, the T cell costimulatory molecule is CD27. In certain embodiments, the T cell costimulatory molecule is OX40. In certain embodiments, the T cell costimulatory molecule is CD40L. In certain embodiments, the T cell costimulatory molecule is HVEM. In certain embodiments, the T cell costimulatory molecule is Galectin-9. In certain embodiments, the T cell costimulatory molecule is TIM-1. In certain embodiments, the T cell costimulatory molecule is LFA1. In certain embodiments, the T cell costimulatory molecule is CD2. In certain embodiments, the T cell costimulatory molecule is PD1.


In specific embodiments of the methods provided herein, the method uses multi-marker detection. In some embodiments, the multi-marker detection uses a multispecific CD4 antibody provided herein. In some embodiments, the multi-marker detection uses a bispecific CD4 antibody provided herein. In some embodiments, the multi-marker detection uses a trispecific CD4 antibody provided herein. In some embodiments, the multi-marker detection uses a quadraspecific CD4 antibody provided herein.


In certain embodiments of the methods provided herein, the methods are included as steps in a diagnostic method. In certain embodiments of the methods provided herein, the methods are included as steps in a method to quantify the CD4-expressing T cells.


In certain embodiments of the methods provided herein, the method further comprises expanding the enriched, isolated, separated, purified, sorted, selected, captured or detected CD4-expressing cells. In certain embodiments, the expanding is in vitro. In certain embodiments, the expanding is in vivo. In certain embodiments of the methods provided herein, the method further comprises growing the enriched, isolated, separated, purified, sorted, selected, captured or detected CD4-expressing cells. In certain embodiments, the growing is in vitro. In certain embodiments, the growing is in vivo. In certain embodiments of the methods provided herein, the method further comprises quantifying the enriched, isolated, separated, purified, sorted, selected, captured or detected CD4-expressing cells.


In another aspect, the multispecific CD4/CD8 antibodies provided herein are used as agents to detect CD4-expressing cells and/or CD8-expressing cells. Thus, in other methods, provided is a method of detecting a cell expressing CD4 and/or CD8, comprising contacting a cell with a multispecific CD4/CD8 antibody provided herein. In certain embodiments, the detecting is by ELISA. In some embodiments, the detecting is by FACS analysis. Also provided are kits comprising a CD4 antibody provided herein, and instructions for use.


Enrichment, isolation, separation, purification, sorting, selecting, capturing or detecting, or any combination thereof can be done using known technologies such as bead, microfluidics, solid support, columns, and the like. For example, CD4+ T cells, such as T helper cells, may be separated or visualized using known methods when bound to the multispecific CD4/CD8 antibodies provided herein. In addition, for example, CD8+ T cells, such as CTL, may be separated or visualized using known methods when bound to the multispecific CD4/CD8 antibodies provided herein.


The multispecific CD4/CD8 antibodies provided herein can be used to selectively enrich, isolate, separate, purify, sort, select, capture or detect CD4-expressing cells and/or CD8-expressing cells. The multispecific CD4/CD8 antibodies provided herein may be utilized in a bispecific format, e.g. containing a first antigen binding domain that specifically binds CD8 and a second antigen binding domain that specifically binds CD4. In other embodiments, the multispecific CD4/CD8 antibodies provided herein may be utilized in a format that further incorporates a third antigen binding domain that specifically binds a third antigen (e.g., at a trispecific antibody). In other embodiments, the multispecific CD4/CD8 antibodies provided herein may be utilized in a format that further incorporates a fourth antigen binding domain that specifically binds a fourth antigen. (e.g., as a quadraspecific antibody). In some embodiments, the cells comprise CD4-expressing cells. In some embodiments, the cells comprise CD8-expressing cells. In some embodiments, the cells comprise CD4-expressing cells and CD8-expressing cells.


In one aspect, provided herein is a method of enriching CD4-expressing cells and/or CD8-expressing cells comprising: providing a sample comprising the CD4-expressing cells and/or CD8-expressing cells; contacting the sample with a multispecific CD4/CD8 antibody provided herein; and enriching the CD4-expressing cells and/or CD8-expressing cells bound to the multispecific CD4/CD8 antibody. In one aspect, provided herein is a method of isolating CD4-expressing cells and/or CD8-expressing cells comprising: providing a sample comprising the CD4-expressing cells and/or CD8-expressing cells; contacting the sample with a multispecific CD4/CD8 antibody provided herein; and isolating the CD4-expressing cells and/or CD8-expressing cells bound to the multispecific CD4/CD8 antibody. In one aspect, provided herein is a method of separating CD4-expressing cells and/or CD8-expressing cells comprising: providing a sample comprising the CD4-expressing cells and/or CD8-expressing cells; contacting the sample with a multispecific CD4/CD8 antibody provided herein; and separating the CD4-expressing cells and/or CD8-expressing cells bound to the multispecific CD4/CD8 antibody. In one aspect, provided herein is a method of purifying CD4-expressing cells and/or CD8-expressing cells comprising: providing a sample comprising the CD4-expressing cells and/or CD8-expressing cells; contacting the sample with a multispecific CD4/CD8 antibody provided herein; and purifying the CD4-expressing cells and/or CD8-expressing cells bound to the multispecific CD4/CD8 antibody. In one aspect, provided herein is a method of sorting CD4-expressing cells and/or CD8-expressing cells comprising: providing a sample comprising the CD4-expressing cells and/or CD8-expressing cells; contacting the sample with a multispecific CD4/CD8 antibody provided herein; and sorting the CD4-expressing cells and/or CD8-expressing cells bound to the multispecific CD4/CD8 antibody. In one aspect, provided herein is a method of selecting CD4-expressing cells and/or CD8-expressing cells comprising: providing a sample comprising the CD4-expressing cells and/or CD8-expressing cells; contacting the sample with a multispecific CD4/CD8 antibody provided herein; and selecting the CD4-expressing cells and/or CD8-expressing cells bound to the multispecific CD4/CD8 antibody. In one aspect, provided herein is a method of capturing CD4-expressing cells and/or CD8-expressing cells comprising: providing a sample comprising the CD4-expressing cells and/or CD8-expressing cells; contacting the sample with a multispecific CD4/CD8 antibody provided herein; and capturing the CD4-expressing cells and/or CD8-expressing cells bound to the multispecific CD4/CD8 antibody. In one aspect, provided herein is a method of detecting CD4-expressing cells and/or CD8-expressing cells comprising: providing a sample comprising the CD4-expressing cells and/or CD8-expressing cells; contacting the sample with a multispecific CD4/CD8 antibody provided herein; and detecting the CD4-expressing cells and/or CD8-expressing cells bound to the multispecific CD4/CD8 antibody. In some embodiments, the cells comprise CD4-expressing cells. In some embodiments, the cells comprise CD8-expressing cells. In some embodiments, the cells comprise CD4-expressing cells and CD8-expressing cells.


In one aspect, provided herein is a method of enriching CD4-expressing cells and/or CD8-expressing cells comprising: contacting CD4-expressing cells and/or CD8-expressing cells with a multispecific CD4/CD8 antibody provided herein; and enriching the CD4-expressing cells and/or CD8-expressing cells bound to the multispecific CD4/CD8 antibody. In one aspect, provided herein is a method of isolating CD4-expressing cells and/or CD8-expressing cells comprising: contacting CD4-expressing cells and/or CD8-expressing cells with a multispecific CD4/CD8 antibody provided herein; and isolating the CD4-expressing cells and/or CD8-expressing cells bound to the multispecific CD4/CD8 antibody. In one aspect, provided herein is a method of separating CD4-expressing cells and/or CD8-expressing cells comprising: contacting CD4-expressing cells and/or CD8-expressing cells with a multispecific CD4/CD8 antibody provided herein; and separating the CD4-expressing cells and/or CD8-expressing cells bound to the multispecific CD4/CD8 antibody. In one aspect, provided herein is a method of purifying CD4-expressing cells and/or CD8-expressing cells comprising: contacting CD4-expressing cells and/or CD8-expressing cells with a multispecific CD4/CD8 antibody provided herein; and purifying the CD4-expressing cells and/or CD8-expressing cells bound to the multispecific CD4/CD8 antibody. In one aspect, provided herein is a method of sorting CD4-expressing cells and/or CD8-expressing cells comprising: contacting CD4-expressing cells and/or CD8-expressing cells with a multispecific CD4/CD8 antibody provided herein; and sorting the CD4-expressing cells and/or CD8-expressing cells bound to the multispecific CD4/CD8 antibody. In one aspect, provided herein is a method of selecting CD4-expressing cells and/or CD8-expressing cells comprising: contacting CD4-expressing cells and/or CD8-expressing cells with a multispecific CD4/CD8 antibody provided herein; and selecting the CD4-expressing cells and/or CD8-expressing cells bound to the multispecific CD4/CD8 antibody. In one aspect, provided herein is a method of capturing CD4-expressing cells and/or CD8-expressing cells comprising: contacting CD4-expressing cells and/or CD8-expressing cells with a multispecific CD4/CD8 antibody provided herein; and capturing the CD4-expressing cells and/or CD8-expressing cells bound to the multispecific CD4/CD8 antibody. In one aspect, provided herein is a method of detecting CD4-expressing cells and/or CD8-expressing cells comprising: contacting CD4-expressing cells and/or CD8-expressing cells with a multispecific CD4/CD8 antibody provided herein; and detecting the CD4-expressing cells and/or CD8-expressing cells bound to the multispecific CD4/CD8 antibody. In some embodiments, the cells comprise CD4-expressing cells. In some embodiments, the cells comprise CD8-expressing cells. In some embodiments, the cells comprise CD4-expressing cells and CD8-expressing cells.


In one aspect, provided herein is a method of enriching CD4-expressing cells and/or CD8-expressing cells comprising: contacting CD4-expressing cells and/or CD8-expressing cells with a multispecific CD4/CD8 antibody provided herein; and enriching the CD4-expressing cells and/or CD8-expressing cells based on binding of the CD4-expressing cells and/or CD8-expressing cells to the multispecific CD4/CD8 antibody. In one aspect, provided herein is a method of isolating CD4-expressing cells and/or CD8-expressing cells comprising: contacting CD4-expressing cells and/or CD8-expressing cells with a multispecific CD4/CD8 antibody provided herein; and isolating the CD4-expressing cells and/or CD8-expressing cells based on binding of the CD4-expressing cells and/or CD8-expressing cells to the multispecific CD4/CD8 antibody. In one aspect, provided herein is a method of separating CD4-expressing cells and/or CD8-expressing cells comprising: contacting CD4-expressing cells and/or CD8-expressing cells with a multispecific CD4/CD8 antibody provided herein; and separating the CD4-expressing cells and/or CD8-expressing cells based on binding of the CD4-expressing cells and/or CD8-expressing cells to the multispecific CD4/CD8 antibody. In one aspect, provided herein is a method of purifying CD4-expressing cells and/or CD8-expressing cells comprising: contacting CD4-expressing cells and/or CD8-expressing cells with a multispecific CD4/CD8 antibody provided herein; and purifying the CD4-expressing cells and/or CD8-expressing cells based on binding of the CD4-expressing cells and/or CD8-expressing cells to the multispecific CD4/CD8 antibody. In one aspect, provided herein is a method of sorting CD4-expressing cells and/or CD8-expressing cells comprising: contacting CD4-expressing cells and/or CD8-expressing cells with a multispecific CD4/CD8 antibody provided herein; and sorting the CD4-expressing cells and/or CD8-expressing cells based on binding of the CD4-expressing cells and/or CD8-expressing cells to the multispecific CD4/CD8 antibody. In one aspect, provided herein is a method of selecting CD4-expressing cells and/or CD8-expressing cells comprising: contacting CD4-expressing cells and/or CD8-expressing cells with a multispecific CD4/CD8 antibody provided herein; and selecting the CD4-expressing cells and/or CD8-expressing cells based on binding of the CD4-expressing cells and/or CD8-expressing cells to the multispecific CD4/CD8 antibody. In one aspect, provided herein is a method of capturing CD4-expressing cells and/or CD8-expressing cells comprising: contacting CD4-expressing cells and/or CD8-expressing cells with a multispecific CD4/CD8 antibody provided herein; and capturing the CD4-expressing cells and/or CD8-expressing cells based on binding of the CD4-expressing cells and/or CD8-expressing cells to the multispecific CD4/CD8 antibody. In one aspect, provided herein is a method of detecting CD4-expressing cells and/or CD8-expressing cells comprising: contacting CD4-expressing cells and/or CD8-expressing cells with a multispecific CD4/CD8 antibody provided herein; and detecting the CD4-expressing cells and/or CD8-expressing cells based on binding of the CD4-expressing cells and/or CD8-expressing cells to the multispecific CD4/CD8 antibody. In some embodiments, the cells comprise CD4-expressing cells. In some embodiments, the cells comprise CD8-expressing cells. In some embodiments, the cells comprise CD4-expressing cells and CD8-expressing cells.


In some embodiments of the methods, the CD4-expressing cells and/or CD8-expressing cells are in a population of cells. In some embodiments of the methods, the CD4-expressing cells and/or CD8-expressing cells are in a population of lymphocytes. In some embodiments of the methods, the CD4-expressing cells and/or CD8-expressing cells are in a population of T cells. In some embodiments of the methods, the CD4-expressing cells and/or CD8-expressing cells are provided as a population of cells. In some embodiments of the methods, the CD4-expressing cells and/or CD8-expressing cells are provided as a population of lymphocytes. In some embodiments of the methods, the CD4-expressing cells and/or CD8-expressing cells are provided as a population of T cells. In some embodiments of the methods, the CD4-expressing cells and/or CD8-expressing cells are provided as a sample comprising a population of cells. In some embodiments of the methods, the CD4-expressing cells and/or CD8-expressing cells are provided as a sample comprising a population of lymphocytes. In some embodiments of the methods, the CD4-expressing cells and/or CD8-expressing cells are provided as a sample comprising a population of T cells. In some embodiments of the methods, the sample is a blood sample. In some embodiments of the methods, the sample is a tissue sample. In some embodiments of the methods, the sample is a tissue culture sample. In some embodiments, the cells comprise CD4-expressing cells. In some embodiments, the cells comprise CD8-expressing cells. In some embodiments, the cells comprise CD4-expressing cells and CD8-expressing cells.


In some embodiments of the methods, the multispecific CD4/CD8 antibody is a multispecific CD4/CD8 antibody provided herein. In some embodiments of the methods, the multispecific CD4/CD8 antibody is a bispecific CD4/CD8 antibody provided herein. In some embodiments of the methods, the multispecific CD4/CD8 antibody is a trispecific CD4/CD8 antibody provided herein. In some embodiments of the methods, the multispecific CD4/CD8 antibody is a quadraspecific CD4/CD8 antibody provided herein. In certain embodiments, the first binding domain of the multispecific CD4/CD8 antibody that binds CD8 specifically binds to CD8. In certain embodiments, the second binding domain of the multispecific CD4/CD8 antibody that binds CD4 specifically binds to CD4. In one embodiment, the multispecific CD4/CD8 antibody comprises: (a) a first binding domain that binds CD8, and (b) a second binding domain that binds to CD4. In one embodiment, the multispecific CD4/CD8 antibody comprises: (a) a first binding domain that binds CD8, (b) a second binding domain that binds to CD4, and (c) a third binding domain that binds to a third target. In one embodiment, the multispecific CD4/CD8 antibody comprises: (a) a first binding domain that binds CD8, (b) a second binding domain that binds to CD4, (c) a third binding domain that binds to a third target, and (d) a fourth binding domain that binds to a fourth target. In one embodiment, the multispecific CD4/CD8 antibody comprises: (a) a first binding domain that specifically binds CD8, and (b) a second binding domain that specifically binds to CD4. In one embodiment, the multispecific CD4/CD8 antibody comprises: (a) a first binding domain that specifically binds CD8, and (b) a second binding domain that specifically binds to CD4, and (c) a third binding domain that specifically binds to a third target. In one embodiment, the multispecific CD4/CD8 antibody comprises: (a) a first binding domain that specifically binds CD8, and (b) a second binding domain that specifically binds to CD4, (c) a third binding domain that specifically binds to a third target, and (d) a fourth binding domain that specifically binds to a fourth target.


In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is not a CD8 antigen. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the fourth target is not a CD8 antigen. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is not a CD8 antigen, and the fourth target is not a CD8 antigen. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is not a CD4 antigen. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the fourth target is not a CD4 antigen. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is not a CD4 antigen, and the fourth target is not a CD4 antigen. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is not a CD8 epitope. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the fourth target is not a CD8 epitope. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is not a CD8 epitope, and the fourth target is not a CD8 epitope. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is not a CD4 epitope. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the fourth target is not a CD4 epitope. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is not a CD4 epitope, and the fourth target is not a CD4 epitope.


In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is a TCR complex. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is CD3. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is CD3ε. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is CD3γ. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is CD3δ. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is CD3ζ. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is a TCRα chain. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is a TCRβ chain. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is a TCRγ chain. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is a TCRδ chain. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is a T cell costimulatory molecule. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is CD28. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is CTLA4. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is ICOS. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is 4-1BB. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is GITR. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is CD27. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is OX40. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is CD40L. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is HVEM. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is Galectin-9. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is TIM-1. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is LFA1. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is CD2. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is PD1.


In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the fourth target is a TCR complex. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the fourth target is CD3. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the fourth target is CD3ε. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the fourth target is CD3γ. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the fourth target is CD3δ. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the fourth target is CD3ζ. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the fourth target is a TCRα chain. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the fourth target is a TCRβ chain. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the fourth target is a TCRγ chain. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the fourth target is a TCRδ chain. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the fourth target is a T cell costimulatory molecule. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the fourth target is CD28. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the fourth target is CTLA4. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the fourth target is ICOS. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the fourth target is 4-1BB. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the fourth target is GITR. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the fourth target is CD27. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the fourth target is OX40. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the fourth target is CD40L. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the fourth target is HVEM. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the fourth target is Galectin-9. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the fourth target is TIM-1. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the fourth target is LFA1. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the fourth target is CD2. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the fourth target is PD1.


In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is a TCR complex, and the fourth target is a T cell costimulatory molecule. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is CD3, and the fourth target is a T cell costimulatory molecule. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is CD3ε, and the fourth target is a T cell costimulatory molecule. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is CD3γ, and the fourth target is a T cell costimulatory molecule. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is CD3δ, and the fourth target is a T cell costimulatory molecule. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is CD3ζ, and the fourth target is a T cell costimulatory molecule. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is a TCRα chain, and the fourth target is a T cell costimulatory molecule. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is a TCRβ chain, and the fourth target is a T cell costimulatory molecule. In some embodiments of the methods, the antibody is a multispecific CD4/CD8 antibody, and the third target is a TCRγ chain, and the fourth target is a T cell costimulatory molecule. In certain embodiments, the T cell costimulatory molecule is CD28. In certain embodiments, the T cell costimulatory molecule is CTLA4. In certain embodiments, the T cell costimulatory molecule is ICOS. In certain embodiments, the T cell costimulatory molecule is 4-1BB. In certain embodiments, the T cell costimulatory molecule is GITR. In certain embodiments, the T cell costimulatory molecule is CD27. In certain embodiments, the T cell costimulatory molecule is OX40. In certain embodiments, the T cell costimulatory molecule is CD40L. In certain embodiments, the T cell costimulatory molecule is HVEM. In certain embodiments, the T cell costimulatory molecule is Galectin-9. In certain embodiments, the T cell costimulatory molecule is TIM-1. In certain embodiments, the T cell costimulatory molecule is LFA1. In certain embodiments, the T cell costimulatory molecule is CD2. In certain embodiments, the T cell costimulatory molecule is PD1.


In a specific embodiment, the target is from a mammal. In a specific embodiment, the target is from a rat. In a specific embodiment, the target is from a mouse. In a specific embodiment, the target is from a primate. In a specific embodiment, the target is from a human.


In specific embodiments of the methods provided herein, the method uses multi-marker detection. In some embodiments, the multi-marker detection uses a multispecific CD4/CD8 antibody provided herein. In some embodiments, the multi-marker detection uses a bispecific CD4/CD8 antibody provided herein. In some embodiments, the multi-marker detection uses a trispecific CD4/CD8 antibody provided herein. In some embodiments, the multi-marker detection uses a quadraspecific CD4/CD8 antibody provided herein.


In certain embodiments of the methods provided herein, the methods are included as steps in a diagnostic method. In certain embodiments of the methods provided herein, the methods are included as steps in a method to quantify the CD4-expressing cells and/or CD8-expressing cells.


In certain embodiments of the methods provided herein, the method further comprises expanding the enriched, isolated, separated, purified, sorted, selected, captured or detected CD4-expressing cells or CD8-expressing cells. In certain embodiments, the expanding is in vitro. In certain embodiments, the expanding is in vivo. In certain embodiments of the methods provided herein, the method further comprises growing the enriched, isolated, separated, purified, sorted, selected, captured or detected CD4-expressing cells or CD8-expressing cells. In certain embodiments, the growing is in vitro. In certain embodiments, the growing is in vivo. In certain embodiments of the methods provided herein, the method further comprises quantifying the enriched, isolated, separated, purified, sorted, selected, captured or detected CD4-expressing cells or CD8-expressing cells.


In some embodiments of the methods provided herein, the method is conducted in suspension. In some embodiments of the methods provided herein, the method is conducted on a solid support.


In some embodiments of the methods provided herein, the method is conducted using beads. In some embodiments of the methods provided herein, the method is conducted using microfluidics. In some embodiments of the methods provided herein, the method is conducted using fluorescent cell sorting. In some embodiments of the methods provided herein, the method is conducted using fluorescence activated cell sorting (FACS). In some embodiments of the methods provided herein, the method is conducted using magnetic bead-based assays (MACS). In some embodiments of the methods provided herein, the method is conducted using a chip. In some embodiments of the methods provided herein, the method is conducted using a column. In some embodiments of the methods provided herein, the method is conducted using a surface. In some embodiments of the methods provided herein, the method is conducted using microfluidics. In some embodiments of the methods provided herein, the method is conducted using microfluidics in combination with a chip. In some embodiments of the methods provided herein, the method is conducted in a single channel. In some embodiments of the methods provided herein, the method is conducted in multiple channels.


In certain embodiments of the methods provided herein, the methods are included as steps in isolating T cells from a patient. In certain embodiments, the patient is a mammal. In specific embodiments, the patient is a human.


EMBODIMENTS

This invention provides the following non-limiting embodiments.


In one set of embodiments, provided are:

    • 1. An antibody that binds CD8, comprising:
      • (1) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:31; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:32;
      • (2) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:65; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:66;
      • (3) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:99; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:100;
      • (4) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:133; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:134;
      • (5) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:167; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:168;
      • (6) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:201; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:202;
      • (7) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:235; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:236;
      • (8) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:269; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:270;
      • (9) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:303; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:304;
      • (10) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:337; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:338;
      • (11) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:371; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:372;
      • (12) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:405; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:406;
      • (13) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:439; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:440;
      • (14) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:473; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:474;
      • (15) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:507; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:508;
      • (16) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:541; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:542;
      • (17) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:575; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:576;
      • (18) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:609; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:610;
      • (19) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:643; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:644;
      • (20) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:677; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:678;
      • (21) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:711; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:712;
      • (22) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:745; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:746;
      • (23) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:779; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:780;
      • (24) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:813; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:814;
      • (25) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:847; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:848;
      • (26) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:881; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:882;
      • (27) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:915; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:916;
      • (28) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:949; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:950;
      • (29) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:983; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:984;
      • (30) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1017; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1018;
      • (31) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1051; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1052;
      • (32) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1085; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1086;
      • (33) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1119; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1120;
      • (34) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1153; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1154;
      • (35) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1187; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1188;
      • (36) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1221; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1222;
      • (37) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1255; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1256;
      • (38) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1289; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1290;
      • (39) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1323; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1324;
      • (40) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1357; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1358;
      • (41) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1391; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1392;
      • (42) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1425; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1426;
      • (43) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1459; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1460;
      • (44) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1493; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1494;
      • (45) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1527; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1528;
      • (46) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1561; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1562;
      • (47) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1595; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1596;
      • (48) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1629; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1630;
      • (49) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1663; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1664;
      • (50) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1697; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1698;
      • (51) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1731; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1732;
      • (52) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1765; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1766;
      • (53) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1799; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1800;
      • (54) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1833; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1834;
      • (55) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1867; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1868;
      • (56) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1901; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1902;
      • (57) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1935; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1936;
      • (58) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1969; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1970;
      • (59) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2003; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2004;
      • (60) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2037; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2038;
      • (61) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2071; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2072;
      • (62) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2105; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2106;
      • (63) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2139; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2140; or
      • (64) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2173; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2174.
    • 2. The antibody of embodiment 1, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the Kabat numbering system.
    • 3. The antibody of embodiment 1, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the Chothia numbering system.
    • 4. The antibody of embodiment 1, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the AbM numbering system.
    • 5. The antibody of embodiment 1, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the Contact numbering system.
    • 6. The antibody of embodiment 1, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the IMGT numbering system.
    • 7. The antibody of any one of embodiments 1 to 6, wherein the antibody is a humanized antibody.
    • 8. The antibody of any one of embodiments 1 to 7, wherein the antibody is an IgG antibody.
    • 9. The antibody of embodiment 8, wherein the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody.
    • 10. The antibody of any one of embodiments 1 to 9, wherein the antibody comprises a kappa light chain.
    • 11. The antibody of any one of embodiments 1 to 9, wherein the antibody comprises a lambda light chain.
    • 12. The antibody of any one of embodiments 1 to 11, wherein the antibody is a monoclonal antibody.
    • 13. The antibody of any one of embodiments 1 to 12, wherein the antibody binds a CD8 antigen.
    • 14. The antibody of any one of embodiments 1 to 12, wherein antibody binds a CD8 epitope.
    • 15. The antibody of any one of embodiments 1 to 14, wherein the antibody specifically binds to CD8.
    • 16. The antibody of any one of embodiments 1 to 15, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 form a binding site for an antigen of the CD8.
    • 17. The antibody of any one of embodiments 1 to 15, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 form a binding site for an epitope of the CD8.
    • 18. The antibody of any one of embodiments 1 to 17, wherein the CD8 is present on the surface of a T cell.
    • 19. An antibody of any one of embodiments 1 to 11, wherein the antibody binds to CD8α.
    • 20. The antibody of embodiment 19, wherein the antibody binds a CD8α antigen.
    • 21. The antibody of embodiment 19, wherein the antibody binds a CD8α epitope.
    • 22. The antibody of any one of embodiments 19 to 21, wherein the antibody specifically binds to CD8.
    • 23. The antibody of any one of embodiments 19 to 22, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 form a binding site for an antigen of the CD8α.
    • 24. The antibody of any one of embodiments 19 to 22, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 form a binding site for an epitope of the CD8α.
    • 25. The antibody of any one of embodiments 19 to 24, wherein the CD8α is present on the surface of a T cell.
    • 26. An antibody of any one of embodiments 1 to 11, wherein the antibody binds to CD8β.
    • 27. The antibody of embodiment 26, wherein the antibody binds a CD8β antigen.
    • 28. The antibody of embodiment 26, wherein the antibody binds a CD8β epitope.
    • 29. The antibody of any one of embodiments 26 to 28, wherein the antibody specifically binds to CD8.
    • 30. The antibody of any one of embodiments 26 to 29, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 form a binding site for an antigen of the CD8β.
    • 31. The antibody of any one of embodiments 26 to 29, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 form a binding site for an epitope of the CD8β.
    • 32. The antibody of any one of embodiments 26 to 29, wherein the CD8β is present on the surface of a T cell.
    • 33. An antibody of any one of embodiments 1 to 11, wherein the antibody binds at the interface of CD8α and CD8β.
    • 34. The antibody of embodiment 33, wherein the antibody binds an antigen at the interface of CD8α and CD8β.
    • 35. The antibody of embodiment 33, wherein the antibody binds an epitope at the interface of CD8α and CD8β.
    • 36. The antibody of any one of embodiments 33 to 35, wherein the antibody specifically binds at the interface of CD8α and CD8β.
    • 37. The antibody of any one of embodiments 33 to 36, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 form a binding site for an antigen at the interface of CD8α and CD8β.
    • 38. The antibody of any one of embodiments 33 to 36, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 form a binding site for an epitope at the interface of CD8α and CD8β.
    • 39. The antibody of any one of embodiments 33 to 38, wherein the interface of CD8α and CD8β is present on the surface of a T cell.
    • 40. The antibody of any one of embodiments 1 to 39, wherein the antibody is multivalent.
    • 41. The antibody of embodiment 40, wherein the antibody is capable of binding at least three antigens.
    • 42. The antibody of embodiment 40, wherein the bispecific antibody is capable of binding at least five antigens.
    • 43. The antibody of any one of embodiments 1 to 42, wherein the antibody is a multispecific antibody.
    • 44. The antibody of embodiment 43, wherein the antibody is a bispecific antibody.
    • 45. The multispecific CD8 antibody of embodiment 43, wherein the multispecific CD8 antibody comprises:
      • (i) a first binding domain that binds CD8, and a second binding domain that binds to a second target;
      • (ii) a first binding domain that binds CD8, a second binding domain that binds to a second target, and a third binding domain that binds to a third target; or
      • (iii) a first binding domain that binds CD8, and a second binding domain that binds to a second target, a third binding domain that binds to a third target, and a fourth binding domain that binds to a fourth target.
    • 46. The multispecific CD8 antibody of embodiment 45, wherein the second target is CD4.
    • 47. The multispecific antibody of embodiment 45, wherein the second target is a T cell receptor (TCR) complex, CD3, CD3ε, CD3γ, CD3δ, CD3ζ, a TCRα chain, a TCRβ chain, a TCRγ chain, or a TCRδ chain.
    • 48. The multispecific CD8 antibody of embodiment 45, wherein the second target is a T cell costimulatory molecule, CD28, CTLA4, ICOS, 4-1BB, GITR, CD27, OX40, CD40L, HVEM, Galectin-9, TIM-1, LFA1, CD2, or PD1.
    • 49. The multispecific CD8 antibody of embodiment 45, wherein the second target is CD4; and wherein the third target is a TCR complex, CD3, CD3ε, CD3γ, CD3δ, CD3ζ, a TCRα chain, a TCRβ chain, a TCRγ chain, a TCRδ chain.
    • 50. The multispecific CD8 antibody of embodiment 45, wherein the second target is CD4; and wherein the third target is a T cell costimulatory molecule, CD28, CTLA4, ICOS, 4-1BB, GITR, CD27, OX40, CD40L, HVEM, Galectin-9, TIM-1, LFA1, CD2, or PD1.
    • 51. The multispecific CD8 antibody of embodiment 45, wherein the second target is a TCR complex, CD3, CD3ε, CD3γ, CD3δ, CD3ζ, a TCRα chain, a TCRβ chain, a TCRγ chain, or a TCRδ chain; and wherein the third target is a T cell costimulatory molecule, CD28, CTLA4, ICOS, 4-1BB, GITR, CD27, OX40, CD40L, HVEM, Galectin-9, TIM-1, LFA1, CD2, or PD1.
    • 52. The multispecific CD8 antibody of embodiment 45, wherein the second target is CD4; wherein the third target is a TCR complex, CD3, CD3ε, CD3γ, CD3δ, CD3ζ, a TCRα chain, a TCRβ chain, a TCRγ chain, or a TCRδ chain; and wherein the fourth target is a T cell costimulatory molecule, CD28, CTLA4, ICOS, 4-1BB, GITR, CD27, OX40, CD40L, HVEM, Galectin-9, TIM-1, LFA1, CD2, or PD1.
    • 53. The multispecific CD8 antibody of embodiment 43, wherein the multispecific CD8 antibody comprises: a first binding domain that binds CD8, and a second binding domain that binds to a second target, a third binding domain that binds to a third target, and a fourth binding domain that binds to a fourth target.
    • 54. The multispecific CD8 antibody of embodiment 53, wherein the second target is CD4, the third target is a TCR complex, and the fourth target is a T cell costimulatory molecule.
    • 55. The multispecific antibody of embodiment 54, wherein the third target is CD3.
    • 56. The multispecific antibody of embodiment 54, wherein the third target is CD3ε.
    • 57. The multispecific antibody of embodiment 54, wherein the third target is CD3γ.
    • 58. The multispecific antibody of embodiment 54, wherein the third target is CD3δ.
    • 59. The multispecific antibody of embodiment 54, wherein the third target is CD3ζ.
    • 60. The multispecific antibody of embodiment 54, wherein the third target is a TCRα chain.
    • 61. The multispecific antibody of embodiment 54, wherein the third target is a TCRβ chain.
    • 62. The multispecific antibody of embodiment 54, wherein the third target is a TCRγ chain.
    • 63. The multispecific antibody of embodiment 54, wherein the third target is a TCRδ chain.
    • 64. The multispecific antibody of any one of embodiments 54 to 63, wherein the fourth target is CD28.
    • 65. The multispecific antibody of any one of embodiments 54 to 63, wherein the fourth target is CTLA4.
    • 66. The multispecific antibody of any one of embodiments 54 to 63, wherein the fourth target is ICOS.
    • 67. The multispecific antibody of any one of embodiments 54 to 63, wherein the fourth target is 4-1BB.
    • 68. The multispecific antibody of any one of embodiments 54 to 63, wherein the fourth target is GITR.
    • 69. The multispecific antibody of any one of embodiments 54 to 63, wherein the fourth target is CD27.
    • 70. The multispecific antibody of any one of embodiments 54 to 63, wherein the fourth target is OX40.
    • 71. The multispecific antibody of any one of embodiments 54 to 63, wherein the fourth target is CD40L.
    • 72. The multispecific antibody of any one of embodiments 54 to 63, wherein the fourth target is HVEM.
    • 73. The multispecific antibody of any one of embodiments 54 to 63, wherein the fourth target is Galectin-9.
    • 74. The multispecific antibody of any one of embodiments 54 to 63, wherein the fourth target is TIM-1.
    • 75. The multispecific antibody of any one of embodiments 54 to 63, wherein the fourth target is LFA1.
    • 76. The multispecific antibody of any one of embodiments 54 to 63, wherein the fourth target is CD2.
    • 77. The multispecific antibody of any one of embodiments 54 to 63, wherein the fourth target is PD1.
    • 78. The multispecific CD8 antibody of embodiment 43, wherein the multispecific CD8 antibody comprises: a first binding domain that binds CD8, and a second binding domain that binds to CD4.
    • 79. The multispecific antibody of embodiment 43, wherein the multispecific CD8 antibody comprises a first binding domain that binds CD8, a second binding domain that binds to a second target, and a third binding domain that binds to a third target.
    • 80. The multispecific CD8 antibody of embodiment 79, wherein the second target is a TCR complex, and the third target is a T cell costimulatory molecule.
    • 81. The multispecific antibody of embodiment 80, wherein the second target is CD3.
    • 82. The multispecific antibody of embodiment 80, wherein the second target is CD3ε.
    • 83. The multispecific antibody of embodiment 80, wherein the second target is CD3γ.
    • 84. The multispecific antibody of embodiment 80, wherein the second target is CD3δ.
    • 85. The multispecific antibody of embodiment 80, wherein the second target is CD3ζ.
    • 86. The multispecific antibody of embodiment 80, wherein the second target is a TCRα chain.
    • 87. The multispecific antibody of embodiment 80, wherein the second target is a TCRβ chain.
    • 88. The multispecific antibody of embodiment 80, wherein the second target is a TCRγ chain.
    • 89. The multispecific antibody of embodiment 80, wherein the second target is a TCRδ chain.
    • 90. The multispecific antibody of any one of embodiments 80 to 89, wherein the third target is CD28.
    • 91. The multispecific antibody of any one of embodiments 80 to 89, wherein the third target is CTLA4.
    • 92. The multispecific antibody of any one of embodiments 80 to 89, wherein the third target is ICOS.
    • 93. The multispecific antibody of any one of embodiments 80 to 89, wherein the third target is 4-1BB.
    • 94. The multispecific antibody of any one of embodiments 80 to 89, wherein the third target is GITR.
    • 95. The multispecific antibody of any one of embodiments 80 to 89, wherein the third target is CD27.
    • 96. The multispecific antibody of any one of embodiments 80 to 89, wherein the third target is OX40.
    • 97. The multispecific antibody of any one of embodiments 80 to 89, wherein the third target is CD40L.
    • 98. The multispecific antibody of any one of embodiments 80 to 89, wherein the third target is HVEM.
    • 99. The multispecific antibody of any one of embodiments 80 to 89, wherein the third target is Galectin-9.
    • 100. The multispecific antibody of any one of embodiments 80 to 89, wherein the third target is TIM-1.
    • 101. The multispecific antibody of any one of embodiments 80 to 89, wherein the third target is LFA1.
    • 102. The multispecific antibody of any one of embodiments 80 to 89, wherein the third target is CD2.
    • 103. The multispecific antibody of any one of embodiments 80 to 89, wherein the third target is PD1.
    • 104. A nucleic acid encoding the antibody of any one of embodiments 1 to 103.
    • 105. A vector comprising the nucleic acid of embodiment 104.
    • 106. A host cell comprising the vector of embodiment 105.
    • 107. A kit comprising the vector of embodiment 105 and packaging for the same.
    • 108. A kit comprising the antibody of any one of embodiments 1 to 103 and packaging for the same.
    • 109. A pharmaceutical composition comprising the antibody of any one of embodiments 1 to 103, and a pharmaceutically acceptable carrier.
    • 110. A method of producing the pharmaceutical composition of embodiment 109, comprising combining the antibody with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition.
    • 111. A method of activating a T cell expressing CD8, comprising contacting the T cell with the antibody of any one of embodiments 1 to 103.
    • 112. The method of embodiment 111, wherein the contacting results in an increase in CD69, CD25, and/or Granzyme B expression, as compared to a control T cell expressing CD8.
    • 113. A method of enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting a CD8-expressing cell comprising: providing a sample comprising the CD8-expressing cell; contacting the sample with the CD8 antibody of any one of embodiments 1 to 103; and enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD8-expressing cell bound to the CD8 antibody.
    • 114. A method of enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting a CD8-expressing cell comprising: contacting a CD8-expressing cell with the CD8 antibody of any one of embodiments 1 to 103; and enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD8-expressing cell bound to the CD8 antibody.
    • 115. A method of enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting a CD8-expressing cell comprising: contacting a CD8-expressing cell with the CD8 antibody of any one of embodiments 1 to 103; and enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD8-expressing cell based on binding of the CD8-expressing cell to the CD8 antibody.
    • 116. The method of any one of embodiments 113 to 115, wherein the CD8-expressing cell is a T cell.
    • 117. The method of any one of embodiments 113 to 116, wherein the CD8-expressing cell is a CD8+ cytotoxic T lymphocyte (CTL).
    • 118. The method of any one of embodiments 113 to 117, wherein the CD8-expressing cell is provided as a sample comprising a population of cells.
    • 119. The method of embodiment 118, wherein the cells are lymphocytes.
    • 120. The method of embodiment 118, wherein the cells are T cells.
    • 121. The method of any one of embodiments 118 to 120, wherein the sample is a blood sample.
    • 122. The method of any one of embodiments 118 to 120, wherein the sample is a tissue sample.
    • 123. An antibody that binds CD4, comprising:
      • (1) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2207; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2208;
      • (2) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2241; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2242;
      • (3) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2275; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2276;
      • (4) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2309; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2310;
      • (5) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2343; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2344;
      • (6) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2377; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2378;
      • (7) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2411; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2412;
      • (8) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2445; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2446;
      • (9) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2479; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2480;
      • (10) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2513; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2514;
      • (11) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2547; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2548;
      • (12) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2581; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2582;
      • (13) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2615; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2616;
      • (14) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2649; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2650;
      • (15) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2683; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2684;
      • (16) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2717; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2718;
      • (17) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2751; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2752;
      • (18) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2785; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2786;
      • (19) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2819; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2820;
      • (20) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2853; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2854;
      • (21) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2887; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2888;
      • (22) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2921; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2922;
      • (23) i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2955; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2956;
      • (24) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2989; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2990;
      • (25) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3023; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3024;
      • (26) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3057; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3058;
      • (27) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3091; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3092;
      • (28) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3125; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3126;
      • (29) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3159; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3160;
      • (30) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3193; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3194;
      • (31) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3227; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3228;
      • (32) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3261; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3262;
      • (33) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3295; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3296;
      • (34) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3329; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3330;
      • (35) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3363; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3364;
      • (36) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3397; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3398;
      • (37) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3431; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3432;
      • (38) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3465; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3466;
      • (39) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3499; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3500;
      • (40) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3533; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3534;
      • (41) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3567; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3568;
      • (42) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3601; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3602;
      • (43) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3635; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3636;
      • (44) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3669; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3670;
      • (45) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3703; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3704;
      • (46) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3737; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3738;
      • (47) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3771; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3772;
      • (48) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3805; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3806;
      • (49) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3839; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3840;
      • (50) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3873; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3874;
      • (51) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3907; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3908;
      • (52) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3941; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3942;
      • (53) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3975; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3976;
      • (54) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4009; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4010;
      • (55) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4043; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4044;
      • (56) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4077; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4078; or
      • (57) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4111; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4112.
      • (58) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4145; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4146;
      • (59) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4179; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4180;
      • (60) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4213; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4214;
      • (61) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4247; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4248;
      • (62) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4281; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4282;
      • (63) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4315; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4316;
      • (64) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4349; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4350;
      • (65) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4383; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4384;
      • (66) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4417; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4418;
      • (67) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4451; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4452;
      • (68) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4485; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4486;
      • (69) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4519; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4520;
      • (70) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4553; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4554;
      • (71) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4587; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4588;
      • (72) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4621; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4622;
      • (73) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4655; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4656;
      • (74) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4689; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4690;
      • (75) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4723; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4724;
      • (76) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4757; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4758;
      • (77) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4791; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4792;
      • (78) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4825; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4826;
      • (79) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4859; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4860;
      • (80) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4893; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4894;
      • (81) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4927; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4928; or
      • (82) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4961; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4962.
    • 124. The antibody of embodiment 123, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the Kabat numbering system.
    • 125. The antibody of embodiment 123, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the Chothia numbering system.
    • 126. The antibody of embodiment 123, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the AbM numbering system.
    • 127. The antibody of embodiment 123, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the Contact numbering system.
    • 128. The antibody of embodiment 123, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the IMGT numbering system.
    • 129. The antibody of any one of embodiments 123 to 128, wherein the antibody is a humanized antibody.
    • 130. The antibody of any one of embodiments 123 to 129, wherein the antibody is an IgG antibody.
    • 131. The antibody of embodiment 130, wherein the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody.
    • 132. The antibody of any one of embodiments 123 to 131, wherein the antibody comprises a kappa light chain.
    • 133. The antibody of any one of embodiments 123 to 131, wherein the antibody comprises a lambda light chain.
    • 134. The antibody of any one of embodiments 123 to 133, wherein the antibody is a monoclonal antibody.
    • 135. The antibody of any one of embodiments 123 to 134, wherein the antibody binds a CD4 antigen.
    • 136. The antibody of any one of embodiments 123 to 134, wherein antibody binds a CD4 epitope.
    • 137. The antibody of any one of embodiments 123 to 135, wherein the antibody specifically binds to CD4.
    • 138. The antibody of any one of embodiments 123 to 137, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 form a binding site for an antigen of the CD4.
    • 139. The antibody of any one of embodiments 123 to 137, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 form a binding site for an epitope of the CD4.
    • 140. The antibody of any one of embodiments 123 to 139, wherein the CD4 is present on the surface of a T cell.
    • 141. The antibody of any one of embodiments 123 to 140, wherein the antibody is multivalent.
    • 142. The antibody of embodiment 141, wherein the antibody is capable of binding at least three antigens.
    • 143. The antibody of embodiment 141, wherein the bispecific antibody is capable of binding at least five antigens.
    • 144. The antibody of any one of embodiments 123 to 143, wherein the antibody is a multispecific antibody.
    • 145. The antibody of embodiment 144, wherein the antibody is a bispecific antibody.
    • 146. The multispecific CD4 antibody of embodiment 144, wherein the multispecific CD4 antibody comprises:
      • (i) a first binding domain that binds CD4, and a second binding domain that binds to a second target;
      • (ii) a first binding domain that binds CD4, a second binding domain that binds to a second target, and a third binding domain that binds to a third target; or
      • (iii) a first binding domain that binds CD4, and a second binding domain that binds to a second target, a third binding domain that binds to a third target, and a fourth binding domain that binds to a fourth target.
    • 147. The multispecific CD4 antibody of embodiment 141, wherein the second target is CD8.
    • 148. The multispecific antibody of embodiment 146, wherein the second target is a T cell receptor (TCR) complex, CD3, CD3ε, CD3γ, CD3δ, CD3ζ, a TCRα chain, a TCRβ chain, a TCRγ chain, or a TCRδ chain.
    • 149. The multispecific CD4 antibody of embodiment 146, wherein the second target is a T cell costimulatory molecule, CD28, CTLA4, ICOS, 4-1BB, GITR, CD27, OX40, CD40L, HVEM, Galectin-9, TIM-1, LFA1, CD2, or PD1.
    • 150. The multispecific CD4 antibody of embodiment 146, wherein the second target is CD8; and wherein the third target is a TCR complex, CD3, CD3ε, CD3γ, CD3δ, CD3ζ, a TCRα chain, a TCRβ chain, a TCRγ chain, a TCRδ chain.
    • 151. The multispecific CD4 antibody of embodiment 146, wherein the second target is CD8; and wherein the third target is a T cell costimulatory molecule, CD28, CTLA4, ICOS, 4-1BB, GITR, CD27, OX40, CD40L, HVEM, Galectin-9, TIM-1, LFA1, CD2, or PD1.
    • 152. The multispecific CD4 antibody of embodiment 146, wherein the second target is a TCR complex, CD3, CD3ε, CD3γ, CD3δ, CD3ζ, a TCRα chain, a TCRβ chain, a TCRγ chain, or a TCRδ chain; and wherein the third target is a T cell costimulatory molecule, CD28, CTLA4, ICOS, 4-1BB, GITR, CD27, OX40, CD40L, HVEM, Galectin-9, TIM-1, LFA1, CD2, or PD1.
    • 153. The multispecific CD4 antibody of embodiment 146, wherein the second target is CD8; wherein the third target is a TCR complex, CD3, CD3ε, CD3γ, CD3δ, CD3ζ, a TCRα chain, a TCRβ chain, a TCRγ chain, or a TCRδ chain; and wherein the fourth target is a T cell costimulatory molecule, CD28, CTLA4, ICOS, 4-1BB, GITR, CD27, OX40, CD40L, HVEM, Galectin-9, TIM-1, LFA1, CD2, or PD1.
    • 154. The multispecific CD4 antibody of embodiment 144, wherein the multispecific CD4 antibody comprises: a first binding domain that binds CD4, and a second binding domain that binds to a second target, a third binding domain that binds to a third target, and a fourth binding domain that binds to a fourth target.
    • 155. The multispecific CD4 antibody of embodiment 154, wherein the second target is CD8, the third target is a TCR complex, and the fourth target is a T cell costimulatory molecule.
    • 156. The multispecific antibody of embodiment 155, wherein the third target is CD3.
    • 157. The multispecific antibody of embodiment 155, wherein the third target is CD3ε.
    • 158. The multispecific antibody of embodiment 155, wherein the third target is CD3γ.
    • 159. The multispecific antibody of embodiment 155, wherein the third target is CD3δ.
    • 160. The multispecific antibody of embodiment 155, wherein the third target is CD3ζ.
    • 161. The multispecific antibody of embodiment 155, wherein the third target is a TCRα chain.
    • 162. The multispecific antibody of embodiment 155, wherein the third target is a TCRβ chain.
    • 163. The multispecific antibody of embodiment 155, wherein the third target is a TCRγ chain.
    • 164. The multispecific antibody of embodiment 155, wherein the third target is a TCRδ chain.
    • 165. The multispecific antibody of any one of embodiments 155 to 164, wherein the fourth target is CD28.
    • 166. The multispecific antibody of any one of embodiments 155 to 164, wherein the fourth target is CTLA4.
    • 167. The multispecific antibody of any one of embodiments 155 to 164, wherein the fourth target is ICOS.
    • 168. The multispecific antibody of any one of embodiments 155 to 164, wherein the fourth target is 4-1BB.
    • 169. The multispecific antibody of any one of embodiments 155 to 164, wherein the fourth target is GITR.
    • 170. The multispecific antibody of any one of embodiments 155 to 164, wherein the fourth target is CD27.
    • 171. The multispecific antibody of any one of embodiments 155 to 164, wherein the fourth target is OX40.
    • 172. The multispecific antibody of any one of embodiments 155 to 164, wherein the fourth target is CD40L.
    • 173. The multispecific antibody of any one of embodiments 155 to 164, wherein the fourth target is HVEM.
    • 174. The multispecific antibody of any one of embodiments 155 to 164, wherein the fourth target is Galectin-9.
    • 175. The multispecific antibody of any one of embodiments 155 to 164, wherein the fourth target is TIM-1.
    • 176. The multispecific antibody of any one of embodiments 155 to 164, wherein the fourth target is LFA1.
    • 177. The multispecific antibody of any one of embodiments 155 to 164, wherein the fourth target is CD2.
    • 178. The multispecific antibody of any one of embodiments 155 to 164, wherein the fourth target is PD1.
    • 179. The multispecific CD4 antibody of embodiment 144, wherein the multispecific CD4 antibody comprises: a first binding domain that binds CD4, and a second binding domain that binds to CD8.
    • 180. The multispecific antibody of embodiment 144, wherein the multispecific CD4 antibody comprises a first binding domain that binds CD4, a second binding domain that binds to a second target, and a third binding domain that binds to a third target.
    • 181. The multispecific CD4 antibody of embodiment 180, wherein the second target is a TCR complex, and the third target is a T cell costimulatory molecule.
    • 182. The multispecific antibody of embodiment 181, wherein the second target is CD3.
    • 183. The multispecific antibody of embodiment 181, wherein the second target is CD3ε.
    • 184. The multispecific antibody of embodiment 181, wherein the second target is CD3γ.
    • 185. The multispecific antibody of embodiment 181, wherein the second target is CD3δ.
    • 186. The multispecific antibody of embodiment 181, wherein the second target is CD3ζ.
    • 187. The multispecific antibody of embodiment 181, wherein the second target is a TCRα chain.
    • 188. The multispecific antibody of embodiment 181, wherein the second target is a TCRβ chain.
    • 189. The multispecific antibody of embodiment 181, wherein the second target is a TCRγ chain.
    • 190. The multispecific antibody of embodiment 181, wherein the second target is a TCRδ chain.
    • 191. The multispecific antibody of any one of embodiments 181 to 190, wherein the third target is CD28.
    • 192. The multispecific antibody of any one of embodiments 181 to 190, wherein the third target is CTLA4.
    • 193. The multispecific antibody of any one of embodiments 181 to 190, wherein the third target is ICOS.
    • 194. The multispecific antibody of any one of embodiments 181 to 190, wherein the third target is 4-1BB.
    • 195. The multispecific antibody of any one of embodiments 181 to 190, wherein the third target is GITR.
    • 196. The multispecific antibody of any one of embodiments 181 to 190, wherein the third target is CD27.
    • 197. The multispecific antibody of any one of embodiments 181 to 190, wherein the third target is OX40.
    • 198. The multispecific antibody of any one of embodiments 181 to 190, wherein the third target is CD40L.
    • 199. The multispecific antibody of any one of embodiments 181 to 190, wherein the third target is HVEM.
    • 200. The multispecific antibody of any one of embodiments 181 to 190, wherein the third target is Galectin-9.
    • 201. The multispecific antibody of any one of embodiments 181 to 190, wherein the third target is TIM-1.
    • 202. The multispecific antibody of any one of embodiments 181 to 190, wherein the third target is LFA1.
    • 203. The multispecific antibody of any one of embodiments 181 to 190, wherein the third target is CD2.
    • 204. The multispecific antibody of any one of embodiments 181 to 190, wherein the third target is PD1.
    • 205. A nucleic acid encoding the antibody of any one of embodiments 123 to 204.
    • 206. A vector comprising the nucleic acid of embodiment 205.
    • 207. A host cell comprising the vector of embodiment 206.
    • 208. A kit comprising the vector of embodiment 206 and packaging for the same.
    • 209. A kit comprising the antibody of any one of embodiments 123 to 204 and packaging for the same.
    • 210. A pharmaceutical composition comprising the antibody of any one of embodiments 113 to 204, and a pharmaceutically acceptable carrier.
    • 211. A method of producing the pharmaceutical composition of embodiment 210, comprising combining the antibody with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition.
    • 212. A method of activating a T cell expressing CD4, comprising contacting the T cell with the antibody of any one of embodiments 123 to 204.
    • 213. The method of embodiment 212, wherein the contacting results in an increase in CD69, CD25, and/or Granzyme B expression, as compared to a control T cell expressing CD4.
    • 214. A method of enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting a CD4-expressing cell comprising: providing a sample comprising the CD4-expressing cell; contacting the sample with the CD4 antibody of any one of embodiments 123 to 204; and enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD4-expressing cell bound to the CD4 antibody.
    • 215. A method of enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting a CD4-expressing cell comprising: contacting a CD4-expressing cell with the CD4 antibody of any one of embodiments 123 to 204; and enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD4-expressing cell bound to the CD4 antibody.
    • 216. A method of enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting a CD4-expressing cell comprising: contacting a CD4-expressing cell with the CD4 antibody of any one of embodiments 123 to 204; and enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD4-expressing cell based on binding of the CD4-expressing cell to the CD4 antibody.
    • 217. The method of any one of embodiments 214 to 216, wherein the CD4-expressing cell is a T cell.
    • 218. The method of any one of embodiments 214 to 217, wherein the CD4-expressing cell is a CD4+ T helper cell.
    • 219. The method of any one of embodiments 214 to 218, wherein the CD4-expressing cell is provided as a sample comprising a population of cells.
    • 220. The method of embodiment 219, wherein the cells are lymphocytes.
    • 221. The method of embodiment 219, wherein the cells are T cells.
    • 222. The method of any one of embodiments 219 to 221, wherein the sample is a blood sample.
    • 223. The method of any one of embodiments 219 to 221, wherein the sample is a tissue sample.
    • 224. A multispecific antibody, wherein the multispecific antibody comprises: a first binding domain that binds to CD8 and a second binding domain that binds to CD4, wherein
      • (A) the first binding domain that binds to CD8 comprises:
        • (1) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:31; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:32;
        • (2) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:65; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:66;
        • (3) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:99; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:100;
        • (4) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:133; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:134;
        • (5) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:167; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:168;
        • (6) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:201; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:202;
        • (7) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:235; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:236;
        • (8) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:269; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:270;
        • (9) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:303; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:304;
        • (10) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:337; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:338;
        • (11) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:371; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:372;
        • (12) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:405; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:406;
        • (13) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:439; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:440;
        • (14) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:473; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:474;
        • (15) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:507; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:508;
        • (16) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:541; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:542;
        • (17) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:575; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:576;
        • (18) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:609; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:610;
        • (19) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:643; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:644;
        • (20) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:677; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:678;
        • (21) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:711; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:712;
        • (22) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:745; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:746;
        • (23) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:779; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:780;
        • (24) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:813; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:814;
        • (25) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:847; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:848;
        • (26) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:881; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:882;
        • (27) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:915; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:916;
        • (28) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:949; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:950;
        • (29) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:983; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:984;
        • (30) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1017; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1018;
        • (31) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1051; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1052;
        • (32) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1085; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1086;
        • (33) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1119; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1120;
        • (34) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1153; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1154;
        • (35) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1187; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1188;
        • (36) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1221; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1222;
        • (37) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1255; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1256;
        • (38) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1289; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1290;
        • (39) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1323; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1324;
        • (40) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1357; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1358;
        • (41) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1391; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1392;
        • (42) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1425; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1426;
        • (43) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1459; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1460;
        • (44) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1493; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1494;
        • (45) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1527; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1528;
        • (46) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1561; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1562;
        • (47) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1595; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1596;
        • (48) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1629; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1630;
        • (49) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1663; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1664;
        • (50) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1697; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1698;
        • (51) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1731; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1732;
        • (52) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1765; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1766;
        • (53) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1799; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1800;
        • (54) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1833; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1834;
        • (55) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1867; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1868;
        • (56) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1901; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1902;
        • (57) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1935; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1936;
        • (58) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1969; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1970;
        • (59) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2003; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2004;
        • (60) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2037; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2038;
        • (61) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2071; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2072;
        • (62) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2105; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2106;
        • (63) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2139; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2140; or
        • (64) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2173; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2174; and
      • (B) the second binding domain that binds to CD4 comprises:
        • (1) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2207; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2208;
        • (2) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2241; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2242;
        • (3) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2275; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2276;
        • (4) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2309; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2310;
        • (5) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2343; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2344;
        • (6) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2377; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2378;
        • (7) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2411; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2412;
        • (8) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2445; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2446;
        • (9) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2479; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2480;
        • (10) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2513; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2514;
        • (11) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2547; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2548;
        • (12) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2581; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2582;
        • (13) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2615; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2616;
        • (14) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2649; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2650;
        • (15) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2683; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2684;
        • (16) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2717; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2718;
        • (17) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2751; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2752;
        • (18) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2785; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2786;
        • (19) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2819; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2820;
        • (20) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2853; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2854;
        • (21) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2887; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2888;
        • (22) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2921; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2922;
        • (23) i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2955; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2956;
        • (24) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2989; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2990;
        • (25) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3023; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3024;
        • (26) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3057; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3058;
        • (27) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3091; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3092;
        • (28) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3125; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3126;
        • (29) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3159; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3160;
        • (30) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3193; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3194;
        • (31) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3227; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3228;
        • (32) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3261; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3262;
        • (33) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3295; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3296;
        • (34) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3329; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3330;
        • (35) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3363; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3364;
        • (36) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3397; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3398;
        • (37) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3431; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3432;
        • (38) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3465; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3466;
        • (39) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3499; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3500;
        • (40) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3533; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3534;
        • (41) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3567; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3568;
        • (42) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3601; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3602;
        • (43) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3635; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3636;
        • (44) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3669; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3670;
        • (45) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3703; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3704;
        • (46) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3737; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3738;
        • (47) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3771; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3772;
        • (48) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3805; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3806;
        • (49) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3839; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3840;
        • (50) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3873; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3874;
        • (51) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3907; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3908;
        • (52) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3941; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3942;
        • (53) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3975; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3976;
        • (54) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4009; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4010;
        • (55) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4043; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4044;
        • (56) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4077; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4078; or
        • (57) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4111; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4112.
        • (58) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4145; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4146;
        • (59) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4179; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4180;
        • (60) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4213; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4214;
        • (61) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4247; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4248;
        • (62) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4281; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4282;
        • (63) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4315; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4316;
        • (64) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4349; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4350;
        • (65) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4383; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4384;
        • (66) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4417; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4418;
        • (67) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4451; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4452;
        • (68) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4485; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4486;
        • (69) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4519; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4520;
        • (70) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4553; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4554;
        • (71) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4587; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4588;
        • (72) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4621; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4622;
        • (73) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4655; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4656;
        • (74) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4689; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4690;
        • (75) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4723; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4724;
        • (76) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4757; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4758;
        • (77) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4791; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4792;
        • (78) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4825; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4826;
        • (79) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4859; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4860;
        • (80) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4893; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4894;
        • (81) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4927; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4928; or
        • (82) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4961; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4962.
    • 225. The multispecific antibody of embodiment 224, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the Kabat numbering system.
    • 226. The multispecific antibody of embodiment 224, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the Chothia numbering system.
    • 227. The multispecific antibody of embodiment 224, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the AbM numbering system.
    • 228. The multispecific antibody of embodiment 224, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the Contact numbering system.
    • 229. The multispecific antibody of embodiment 224, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the IMGT numbering system.
    • 230. The multispecific antibody of any one of embodiments 224 to 229, wherein the antibody is a humanized antibody.
    • 231. The multispecific antibody of any one of embodiments 224 to 230, wherein the antibody is an IgG antibody.
    • 232. The multispecific antibody of embodiment 231, wherein the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody.
    • 233. The multispecific antibody of any one of embodiments 224 to 232, wherein the antibody comprises a kappa light chain.
    • 234. The multispecific antibody of any one of embodiments 224 to 232, wherein the antibody comprises a lambda light chain.
    • 235. The multispecific antibody of any one of embodiments 224 to 234, wherein the antibody is a monoclonal antibody.
    • 236. The multispecific antibody of any one of embodiments 224 to 235, wherein the first binding domain binds a CD8 antigen.
    • 237. The multispecific antibody of any one of embodiments 224 to 235, wherein the first binding domain binds a CD8 epitope.
    • 238. The multispecific antibody of any one of embodiments 224 to 237, wherein the first binding domain specifically binds to CD8.
    • 239. The multispecific antibody of any one of embodiments 224 to 238, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the first binding domain form a binding site for an antigen of the CD8.
    • 240. The multispecific antibody of any one of embodiments 224 to 238, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the first binding domain form a binding site for an epitope of the CD8.
    • 241. The multispecific antibody of any one of embodiments 224 to 240, wherein the CD8 is present on the surface of a T cell.
    • 242. The multispecific antibody of any one of embodiments 224 to 241, wherein the second binding domain binds a CD4 antigen.
    • 243. The multispecific antibody of any one of embodiments 224 to 241, wherein the second binding domain binds a CD4 epitope.
    • 244. The multispecific antibody of any one of embodiments 224 to 243, wherein the second binding domain specifically binds to CD4.
    • 245. The multispecific antibody of any one of embodiments 224 to 244, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the second binding domain form a binding site for an antigen of the CD4.
    • 246. The multispecific antibody of any one of embodiments 224 to 244, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the second binding domain form a binding site for an epitope of the CD4.
    • 247. The multispecific antibody of any one of embodiments 224 to 246, wherein the CD4 is present on the surface of a T cell.
    • 248. The multispecific antibody of any one of embodiments 224 to 247, wherein the antibody is multivalent.
    • 249. The multispecific antibody of embodiment 248, wherein the antibody is capable of binding at least three antigens.
    • 250. The multispecific antibody of embodiment 248, wherein the antibody is capable of binding at least four antigens.
    • 251. The multispecific antibody of embodiment 248, wherein the antibody is capable of binding at least five antigens.
    • 252. The multispecific antibody of any one of embodiments 224 to 248, wherein the antibody is a bispecific antibody.
    • 253. The multispecific antibody of any one of embodiments 224 to 248, wherein the antibody is a trispecific antibody.
    • 254. The multispecific antibody of any one of embodiments 224 to 248, wherein the antibody is a quadraspecific antibody.
    • 255. The multispecific antibody of any one of embodiments 224 to 248, wherein the multispecific antibody further comprises: a third binding domain that binds to a third target.
    • 256. The multispecific antibody of embodiment 255, wherein the third target is a T Cell Receptor (TCR) complex.
    • 257. The multispecific antibody of embodiment 255, wherein the third target is CD3.
    • 258. The multispecific antibody of embodiment 255, wherein the third target is CD3F.
    • 259. The multispecific antibody of embodiment 255, wherein the third target is CD3γ.
    • 260. The multispecific antibody of embodiment 255, wherein the third target is CD3δ.
    • 261. The multispecific antibody of embodiment 255, wherein the third target is CD3ζ.
    • 262. The multispecific antibody of embodiment 255, wherein the third target is a TCRα chain.
    • 263. The multispecific antibody of embodiment 255, wherein the third target is a TCRβ chain.
    • 264. The multispecific antibody of embodiment 255, wherein the third target is a TCRγ chain.
    • 265. The multispecific antibody of embodiment 255, wherein the third target is a TCRδ chain.
    • 266. The multispecific antibody of any one of embodiments 255 to 265, wherein the multispecific antibody further comprises a fourth binding domain that binds to a fourth target.
    • 267. The multispecific antibody of embodiment 266, wherein the fourth target is CD28.
    • 268. The multispecific antibody of embodiment 266, wherein the fourth target is CTLA4.
    • 269. The multispecific antibody of embodiment 266, wherein the fourth target is ICOS.
    • 270. The multispecific antibody of embodiment 266, wherein the fourth target is 4-1BB.
    • 271. The multispecific antibody of embodiment 266, wherein the fourth target is GITR.
    • 272. The multispecific antibody of embodiment 266, wherein the fourth target is CD27.
    • 273. The multispecific antibody of embodiment 266, wherein the fourth target is OX40.
    • 274. The multispecific antibody of embodiment 266, wherein the fourth target is CD40L.
    • 275. The multispecific antibody of embodiment 266, wherein the fourth target is HVEM.
    • 276. The multispecific antibody of embodiment 266, wherein the fourth target is Galectin-9.
    • 277. The multispecific antibody of embodiment 266, wherein the fourth target is TIM-1.
    • 278. The multispecific antibody of embodiment 266, wherein the fourth target is LFA1.
    • 279. The multispecific antibody of embodiment 266, wherein the fourth target is CD2.
    • 280. The multispecific antibody of embodiment 266, wherein the fourth target is PD1.
    • 281. A nucleic acid encoding the antibody of any one of embodiments 224 to 280.
    • 282. A vector comprising the nucleic acid of embodiment 281.
    • 283. A host cell comprising the vector of embodiment 282.
    • 284. A kit comprising the vector of embodiment 282 and packaging for the same.
    • 285. A kit comprising the antibody of any one of embodiments 224 to 280 and packaging for the same.
    • 286. A pharmaceutical composition comprising the antibody of any one of embodiments 224 to 280, and a pharmaceutically acceptable carrier.
    • 287. A method of producing the pharmaceutical composition of embodiment 286, comprising combining the antibody with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition.
    • 288. A method of enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting CD4-expressing cells and/or CD8-expressing cells comprising: providing a sample comprising the CD4-expressing cells and/or CD8-expressing cells; contacting the sample with the multispecific antibody of any one of embodiments 224 to 280; and enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD4-expressing cells and/or CD8-expressing cells bound to the multispecific antibody.
    • 289. A method of enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting CD4-expressing cells and/or CD8-expressing cells comprising: contacting CD4-expressing cells and/or CD8-expressing cells with the multispecific antibody of any one of embodiments 224 to 280; and enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD4-expressing cells and/or CD8-expressing cells bound to the multispecific antibody.
    • 290. A method of enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting CD4-expressing cells and/or CD8-expressing cells comprising: contacting CD4-expressing cells and/or CD8-expressing cells with the multispecific antibody of any one of embodiments 224 to 280; and enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD4-expressing cells and/or CD8-expressing cells based on binding of the CD4-expressing cells and/or CD8-expressing cells to the multispecific antibody.
    • 291. The method of any one of embodiments 288 to 290, wherein the CD4-expressing cells and/or CD8-expressing cells are T cells.
    • 292. The method of any one of embodiments 288 to 290, wherein the CD4-expressing cells are CD4+ T helper cells.
    • 293. The method of any one of embodiments 288 to 290, wherein the CD8-expressing cells are CD8+ CTL.
    • 294. The method of any one of embodiments 288 to 293, wherein the CD4-expressing cells and/or CD8-expressing cells is provided as a sample comprising a population of cells.
    • 295. The method of embodiment 294, wherein the cells are lymphocytes.
    • 296. The method of embodiment 294, wherein the cells are T cells.
    • 297. The method of any one of embodiments 288 to 296, wherein the sample is a blood sample.
    • 298. The method of any one of embodiments 288 to 296, wherein the sample is a tissue sample.


Provided in the Examples herein are exemplary antibodies that bind to CD8. Exemplary binding agents that bind to CD8 are provided herein, for example in the Examples, as well as Tables 2-7.


In addition, provided in the Examples herein are exemplary antibodies that bind to CD4. Exemplary binding agents that bind to CD4 are provided herein, for example in the Examples, as well as Tables 11-16.


In some embodiments, provided is a multispecific CD4/CD8 antibody comprising a first binding domain that binds to CD8, wherein the first binding domain comprises a VH CDR1, VH CDR2, and VH CDR3 of a CD8 antibody provided in Tables 2-7. In some embodiments, provided is a multispecific CD4/CD8 antibody comprising a first binding domain that binds to CD8, wherein the first binding domain comprises a VL CDR1, VL CDR2, and VL CDR3 of a CD8 antibody provided in Tables 2-7. In some embodiments, provided is a multispecific CD4/CD8 antibody comprising a first binding domain that binds to CD8, wherein the first binding domain comprises a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of a CD8 antibody provided in Tables 2-7. In some embodiments, provided is a multispecific CD4/CD8 antibody comprising a second binding domain that binds to CD4, wherein the second binding domain comprises a VH CDR1, VH CDR2, and VH CDR3 of a CD4 antibody provided in Tables 11-16. In some embodiments, provided is a multispecific CD4/CD4 antibody comprising a second binding domain that binds to CD4, wherein the second binding domain comprises a VL CDR1, VL CDR2, and VL CDR3 of a CD4 antibody provided in Tables 11-16. In some embodiments, provided is a multispecific CD4/CD4 antibody comprising a second binding domain that binds to CD4, wherein the second binding domain comprises a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of a CD4 antibody provided in Tables 11-16.


In some embodiments, provided is a multispecific CD4/CD8 antibody comprising a first binding domain that binds to CD8 and a second binding domain that binds to CD4, wherein the first binding domain that binds to CD8 comprises a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of a CD8 antibody provided in Tables 2-7, and the second binding domain that binds to CD4 comprises a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of a CD4 antibody provided in Tables 11-16. In some embodiments of multispecific CD4/CD8 antibody provided herein, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the Kabat numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the Chothia numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the AbM numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the Contact numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the IMGT numbering system.


Particular embodiments of this invention are described herein. Upon reading the foregoing description, variations of the disclosed embodiments may become apparent to individuals working in the art, and it is expected that those skilled artisans may employ such variations as appropriate. Accordingly, it is intended that the invention be practiced otherwise than as specifically described herein, and that the invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above-described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context. A number of embodiments of the invention have been described. Nevertheless, it will be understood that various modifications may be made without departing from the spirit and scope of the invention. Accordingly, the descriptions in the Examples section are intended to illustrate but not limit the scope of invention described in the claims.


EXAMPLES
Example 1: Production of Antibodies that Bind CD8

1.1: Generation CD8α Antibodies, CD8β Antibodies, and CD8αβ Antibodies


Immunogen.


Recombinant human CD8alpha/beta heterodimer protein (cat #9358-CD) was obtained from R&D Systems, Inc. The amino acid sequence of the heterodimeric protein is listed in Table 1.









TABLE 1







Amino acid sequence of recombinant


human CD8α/β heterodimer protein















SEQ




Protein

ID 



Name
ID
Sequence
NO







Recombinant
rhCD8α
SQFRVSPLDR
4965



human
(Ser22-
TWNLGETVEL




CD8α/β
Asp182)
KCQVLLSNPT




heterodimer
Accession
SGCSWLFQPR




protein
#P01732
GAAASPTFLL




(cat #:

YLSQNKPKAA




9358-CD)

EGLDTQRFSG






KRLGDTFVLT






LSDFRRENEG






YYFCSALSNS






IMYFSHFVPV






FLPAKPTTTP






APRPPTPAPT






IASQPLSLRP






EACRPAAGGA






VHTRGLDFAC






D-






[proprietary






R&D System






acidic tails]-






HHHHHH 






(-HHHHHH Tail






SEQ ID






NO: 4968)









rhCD8β
NSVLQQTPAY
4966




(Asn19-
IKVQTNKMVM





Pro170)
LSCEAKISLS





Accession
NMRIYWLRQR





#P10966
QAPSSDSHHE






FLALWDSAKG






TIHGEEVEQE






KIAVFRDASR






FILNLTSVKP






EDSGIYFCMI






VGSPELTFGK






GTQLSVVDFL






PTTAQPTKKS






TLKKRVCRLP






RPETQKGPLC






SP-






[proprietary






R&D






System basic






tails]-






DYKDDDDK






(-DYKDDDDK






Tail






SEQ ID






NO: 4969)










Immunization in wild-type mouse and screening of anti-CD8α antibodies, anti-CD8β antibodies, and anti-CD8αβ antibodies. Wild-type (WT) mice with 6 different MHC combinations was immunized using rapid immunization protocol. Eight mice were selected for cell fusion based on serum titer. Hybridoma supernatants were screening by LUMINEX® (immunoassay system) using the immunogen and human pan-T cells. Hits were V-region recovered and formatted into monoclonal IgG1 antibodies.


All the monoclonal antibodies were produced as full-length antibodies as human IgG1. Nucleic acid sequences encoding variable regions were subcloned into a custom mammalian expression vectors containing constant region of IgG1 Fc expression cassettes using standard PCR restriction enzyme based cloning techniques. The mAbs were expressed by transient transfection in Chinese hamster ovary cell line. The antibodies were initially purified by MAB SELECT SURE™ Protein A column (GE healthcare, Piscataway, New Jersey) (Brown, Bottomley et al. 1998). The column was equilibrated with Phosphate Buffer Saline (PBS), pH 7.2 and loaded with fermentation supernatant at a flow rate of 2 mL/min. After loading, the column was washed with PBS (4 CV) followed by elution in 30 mM sodium acetate, pH 3.5. Fractions containing protein peaks as monitored by Absorbance at 280 nm in AKTA™ Explorer (preparative chromatography system) (GE healthcare) were pooled together and were neutralized to pH 5.0 by adding 1% of 3 M sodium acetate, pH 9.0. As a polishing step, the antibodies were purified on a preparative size exclusion chromatography (SEC) using a SUPERDEX® 200 column (GE healthcare). The integrity of the sample was assessed by endotoxin measurement and SDS polyacrylamide gel electrophoresis under reducing and non-reducing conditions. The intact mass was confirmed by mass spectrometry.


The VH and VL sequences of certain CD8 antibodies are provided in Table 2. The CDRs sequences of certain CD8 antibodies are provided in Table 3 (Kabat), Table 4 (Chothia), Table 5 (AbM), Table 6 (Contact), and Table 7 (IMGT). Respective SEQ ID NOs are provided below each sequence.









TABLE 2







VH and VL Amino Acid Sequences of CD8 Antibodies















Protein
HC
LC
VH
VL
Heavy Chain
Light Chain


#
Name
Isotype
Isotype
AA sequence
AA sequence
AA sequence
AA sequence

















1
CD8B191
IgG1
Kappa
QIQLVQSGPE
DIVLTQSPAT
QIQLVQSGPE
DIVLTQSPAT






LVKPGTSMKM
LSVTPGDRVS
LVKPGTSMKM
LSVTPGDRVS






SCKASGYTFT
LSCRASQSIS
SCKASGYTFT
LSCRASQSIS






DYYMNWVKQS
DFLHWYQQKS
DYYMNWVKQS
DFLHWYQQKS






HGKSLEWIGR
HESPRLLIKY
HGKSLEWIGR
HESPRLLIKY






VIPSNGGTIY
ASQSISGIPS
VIPSNGGTIY
ASQSISGIPS






NLKFKGKATL
RFSGSGSGSD
NLKFKGKATL
RFSGSGSGSD






TVDKSLSTAY
FTLTINSVEP
TVDKSLSTAY
FTLTINSVEP






MQLNSLTSED
EDVGVYYCQN
MQLNSLTSED
EDVGVYYCQN






SAVYFCARED
GHSFPYTFGS
SAVYFCARED
GHSFPYTFGS






YNNQGFFLDA
GTKLEIK
YNNQGFFLDA
GTKLEIKRTV






MDYWGQGTSV

MDYWGQGTSV
AAPSVFIFPP






TVSS

TVSSASTKGP
SDEQLKSGTA








SVFPLAPSSK
SVVCLLNNFY








STSGGTAALG
PREAKVQWKV








CLVKDYFPEP
DNALQSGNSQ








VTVSWNSGAL
ESVTEQDSKD








TSGVHTFPAV
STYSLSSTLT








LQSSGLYSLS
LSKADYEKHK








SVVTVPSSSL
VYACEVTHQG








GTQTYICNVN
LSSPVTKSFN








HKPSNTKVDK
RGEC








KVEPKSCDKT









HTCPPCPAPE









LLGGPSVFLF









PPKPKDTLMI









SRTPEVTCVV









VDVSHEDPEV









KFNWYVDGVE









VHNAKTKPRE









EQYNSTYRVV









SVLTVLHQDW









LNGKEYKCKV









SNKALPAPIE









KTISKAKGQP









REPQVYTLPP









SREEMTKNQV









SLTCLVKGFY









PSDIAVEWES









NGQPENNYKT









TPPVLDSDGS









FFLYSKLTVD









KSRWQQGNVF









SCSVMHEALH









NHYTQKSLSL









SPGK







  31
  32
  33
  34





2
CD8B226
IgG1
Kappa
EFQLQQSGPE
DIVMTQSPAT
EFQLQQSGPE
DIVMTQSPAT






LVKPGASVKM
LSVTPGDRVS
LVKPGASVKM
LSVTPGDRVS






SCKASGYTFT
LSCRASQSIS
SCKASGYTFT
LSCRASQSIS






DYYMNWVKQS
HYLHWYQQKL
DYYMNWKQSH
HYLHWYQQKL






HGKSLQWIGR
HESPRLLIKY
GKSLQWIGRI
HESPRLLIKY






IIPSNGATIY
ASQSISGIPS
IPSNGATIYN
ASQSISGIPS






NQKFKGKATL
RFSGSGSGSD
QKFKGKATLT
RFSGSGSGSD






TVDKSLSTAY
FTLSINSVEP
VDKSLSTAYM
FTLSINSVEP






MHLNSLTSED
EDVGVYYCQN
HLNSLTSEDS
EDVGVYYCQN






SAVYYCARED
GHSFPYTFGG
AVYYCAREDY
GHSFPYTFGG






YSNQGFFLDA
GTKLEIK
SNQGFFLDAM
GTKLEIKRTV






MDYWGQGTTV

DYWGQGTTVT
AAPSVFIFPP






TVSS

VSSASTKGPS
SDEQLKSGTA








VFPLAPSSKS
SVVCLLNNFY








TSGGTAALGC
PREAKVQWKV








LVKDYFPEPV
DNALQSGNSQ








TVSWNSGALT
ESVTEQDSKD








SGVHTFPAVL
STYSLSSTLT








QSSGLYSLSS
LSKADYEKHK








VVTVPSSSLG
VYACEVTHQG








TQTYICNVNH
LSSPVTKSFN








KPSNTKVDKK
RGEC








VEPKSCDKTH









TCPPCPAPEL









LGGPSVFLFP









PKPKDTLMIS









RTPEVTCVVV









DVSHEDPEVK









FNWYVDGVEV









HNAKTKPREE









QYNSTYRVVS









VLTVLHQDWL









NGKEYKCKVS









NKALPAPIEK









TISKAKGQPR









EPQVYTLPPS









REEMTKNQVS









LTCLVKGFYP









SDIAVEWESN









GQPENNYKTT









PPVLDSDGSF









FLYSKLTVDK









SRWQQGNVFS









CSVMHEALHN









HYTQKSLSLS









PGK







  65
  66
  67
  68





3
CD8B259
IgG1
Kappa
EVQLQQSGPE
DIVMTQSPAT
EVQLQQSGPE
DIVMTQSPAT






LVKPGASVKM
LSVTPGDRVS
LVKPGASVKM
LSVTPGDRVS






SCKASGYTFT
LSCRASQSIS
SCKASGYTFT
LSCRASQSIS






DYYMNWVKQS
HFLHWYQQKS
DYYMNWVKQS
HFLHWYQQKS






HGKSLEWIGR
HESPRLLIKY
HGKSLEWIGR
HESPRLLIKY






VIPSNGGTIY
ASQSISGSPS
VIPSNGGTIY
ASQSISGSPS






NQKFRG

NQKFRGKATL
KFSGSGSGSD








TVDKSLSTAY
FTLTINSVEP








MQLNSLTSED
EDVGVYYCQS








SAVYYCARED
GHSFPYTFGS








YGNQGFFLDA
GTKLEIKRTV








MDYWGQGTTV
AAPSVFIFPP








TVSSASTKGP









SVFPLAPSSK









STSGGTAALG









CLVKDYFPEP









VTVSWNSGAL









TSGVHTFPAV









LQSSGLYSLS









SVVTVPSSSL









GTQTYICNVN









HKPSNTKVDK







KATLTVDKSL
KFSGSGSGSD
KVEPKSCDKT
SDEQLKSGTA






STAYMQLNSL
FTLTINSVEP
HTCPPCPAPE
SVVCLLNNFY






TSEDSAVYYC
EDVGVYYCQS
LLGGPSVFLF
PREAKVQWKV






AREDYGNQGF
GHSFPYTFGS
PPKPKDTLMI
DNALQSGNSQ






FLDAMDYWGQ
GTKLEIK
SRTPEVTCVV
ESVTEQDSKD






GTTVTVSS

VDVSHEDPEV
STYSLSSTLT








KFNWYVDGVE
LSKADYEKHK








VHNAKTKPRE
VYACEVTHQG








EQYNSTYRVV
LSSPVTKSFN








SVLTVLHQDW
RGEC








LNGKEYKCKV









SNKALPAPIE









KTISKAKGQP









REPQVYTLPP









SREEMTKNQV









SLTCLVKGFY









PSDIAVEWES









NGQPENNYKT









TPPVLDSDGS









FFLYSKLTVD









KSRWQQGNVF









SCSVMHEALH









NHYTQKSLSL









SPGK







  99
 100
 101
 102





4
CD8B298
IgG1
Kappa
QVQLQQSGPE
DIVMTQSPAT
QVQLQQSGPE
DIVMTQSPAT






LVKPGASVKM
LSVTPGDRVS
LVKPGASVKM
LSVTPGDRVS






SCKASGYTFT
LSCRASQTIS
SCKASGYTFT
LSCRASQTIS






DYYMNWVKQS
DYLHWYQQKS
DYYMNWVKQS
DYLHWYQQKS






HGKSLEWIGR
HESPRLLIKY
HGKSLEWIGR
HESPRLLIKY






VIPNNGGTRY
ASQSISGIPS
VIPNNGGTRY
ASQSISGIPS






NQKFKGKATL
RFSGSGSGSD
NQKFKGKATL
RFSGSGSGSD






TVDKSLSTAY
FTLSINSVEP
TVDKSLSTAY
FTLSINSVEP






MQLNSLTSED
EDVGVYYCQN
MQLNSLTSED
EDVGVYYCQN






SAVYYCARED
GHSFPYTFGA
SAVYYCARED
GHSFPYTFGA






FSNQGFFLDA
GTKLELK
FSNQGFFLDA
GTKLELKRTV






MDYWGQGTSV

MDYWGQGTSV
AAPSVFIFPP






TVSS

TVSSASTKGP
SDEQLKSGTA








SVFPLAPSSK
SVVCLLNNFY








STSGGTAALG
PREAKVQWKV








CLVKDYFPEP
DNALQSGNSQ








VTVSWNSGAL
ESVTEQDSKD








TSGVHTFPAV
STYSLSSTLT








LQSSGLYSLS
LSKADYEKHK








SVVTVPSSSL
VYACEVTHQG








GTQTYICNVN
LSSPVTKSFN








HKPSNTKVDK
RGEC








KVEPKSCDKT









HTCPPCPAPE









LLGGPSVFLF









PPKPKDTLMI









SRTPEVTCVV









VDVSHEDPEV









KFNWYVDGVE









VHNAKTKPRE









EQYNSTYRVV









SVLTVLHQDW









LNGKEYKCKV









SNKALPAPIE









KTISKAKGQP









REPQVYTLPP









SREEMTKNQV









SLTCLVKGFY









PSDIAVEWES









NGQPENNYKT









TPPVLDSDGS









FFLYSKLTVD









KSRWQQGNVF









SCSVMHEALH









NHYTQKSLSL









SPGK







 133
 134
 135
 136





5
CD8B342
IgG1
Kappa
EFQLQQSGPE
DIVMTQTPAT
EFQLQQSGPE
DIVMTQTPAT






LVKPGASVKV
LSVTPGDRVS
LVKPGASVKV
LSVTPGDRVS






SCKASGYTFT
LSCRASQTIS
SCKASGYTFT
LSCRASQTIS






DYYVNWVQQS
NYLHWYQQKS
DYYVNWVQQS
NYLHWYQQKS






HGKSLEWIGR
HESPRLLIKY
HGKSLEWIGR
HESPRLLIKY






VIPNNGNVIY
ASQSISGIPS
VIPNNGNVIY
ASQSISGIPS






NQNFKGKATL
RFSGSGSGSD
NQNFKGKATL
RFSGSGSGSD






TVDKSLSSAY
FTLSINSVEP
TVDKSLSSAY
FTLSINSVEP






LQLNSLTSED
EDVGVYYCQN
LQLNSLTSED
EDVGVYYCQN






SAVYYCTRED
GHSFPYTFGG
SAVYYCTRED
GHSFPYTFGG






YSNQGFFLDA
GTKLEIK
YSNQGFFLDA
GTKLEIKRTV






MDYWGQGTSV

MDYWGQGTSV
AAPSVFIFPP






TVSS

TVSSASTKGP
SDEQLKSGTA








SVFPLAPSSK
SVVCLLNNFY








STSGGTAALG
PREAKVQWKV








CLVKDYFPEP
DNALQSGNSQ








VTVSWNSGAL
ESVTEQDSKD








TSGVHTFPAV
STYSLSSTLT








LQSSGLYSLS
LSKADYEKHK








SVVTVPSSSL
VYACEVTHQG








GTQTYICNVN
LSSPVTKSFN








HKPSNTKVDK
RGEC








KVEPKSCDKT









HTCPPCPAPE









LLGGPSVFLF









PPKPKDTLMI









SRTPEVTCVV









VDVSHEDPEV









KFNWYVDGVE









VHNAKTKPRE









EQYNSTYRVV









SVLTVLHQDW









LNGKEYKCKV









SNKALPAPIE









KTISKAKGQP









REPQVYTLPP









SREEMTKNQV









SLTCLVKGFY









PSDIAVEWES









NGQPENNYKT









TPPVLDSDGS









FFLYSKLTVD









KSRWQQGNVF









SCSVMHEALH









NHYTQKSLSL









SPGK







 167
 168
 169
 170





6
CD8B364
IgG1
Kappa
QVQLQQPGAE
DIVLTQSPAS
QVQLQQPGAE
DIVLTQSPAS






LVKPGASVKL
LSVATGEKVT
LVKPGASVKL
LSVATGEKVT






SCKASGYTFT
IRCITSTDID
SCKASGYTFT
IRCITSTDID






SYWMHWVNRR
DDMNWYQQKP
SYWMHWVNRR
DDMNWYQQKP






PGQGLEWIGE
GEPPKLLISE
PGQGLEWIGE
GEPPKLLISE






INPSNGDSYY
GNTLRPGVPS
INPSNGDSYY
GNTLRPGVPS






NEKFKRKATL
RFSSSGYGTD
NEKFKRKATL
RFSSSGYGTD






TVDISSSTAY
FVFTIENTLS
TVDISSSTAY
FVFTIENTLS






MQLSSLTSED
EDVADYYCLQ
MQLSSLTSED
EDVADYYCLQ






SAVYYCTRSM
SDNMPLTFGA
SAVYYCTRSM
SDNMPLTFGA






YYDGRAGAYW
GTKLELK
YYDGRAGAYW
GTKLELKRTV






GQGTTVTVSS

GQGTTVTVSS
AAPSVFIFPP








ASTKGPSVFP
SDEQLKSGTA








LAPSSKSTSG
SVVCLLNNFY








GTAALGCLVK
PREAKVQWKV








DYFPEPVTVS
DNALQSGNSQ








WNSGALTSGV
ESVTEQDSKD








HTFPAVLQSS
STYSLSSTLT








GLYSLSSVVT
LSKADYEKHK








VPSSSLGTQT
VYACEVTHQG








YICNVNHKPS
LSSPVTKSFN








NTKVDKKVEP
RGEC








KSCDKTHTCP









PCPAPELLGG









PSVFLFPPKP









KDTLMISRTP









EVTCVVVDVS









HEDPEVKFNW









YVDGVEVHNA









KTKPREEQYN









STYRVVSVLT









VLHQDWLNGK









EYKCKVSNKA









LPAPIEKTIS









KAKGQPREPQ









VYTLPPSREE









MTKNQVSLTC









LVKGFYPSDI









AVEWESNGQP









ENNYKTTPPV









LDSDGSFFLY









SKLTVDKSRW









QQGNVFSCSV









MHEALHNHYT









QKSLSLSPGK







 201
 202
 203
 204





7
CD8B200
IgG1
Kappa
EVQLQQSGAE
DIQMTQTTSS
EVQLQQSGAE
DIQMTQTTSS






LVKPGASVKL
LSASLGDRVT
LVKPGASVKL
LSASLGDRVT






SCKASGYTFT
ITCRASQDIS
SCKASGYTFT
ITCRASQDIS






NYWIHWVKQR
PYLNWYQQKP
NYWIHWVKQR
PYLNWYQQKP






PGQGLEWIGN
EGTIKLLIYY
PGQGLEWIGN
EGTIKLLIYY






IDPSDSETHY
TSKLHSGVPS
IDPSDSETHY
TSKLHSGVPS






NQKFKDKATL
RFSGSGSGTD
NQKFKDKATL
RFSGSGSGTD






TVDKSSSTAY
YSLTISNLEQ
TVDKSSSTAY
YSLTISNLEQ






MQLISLTSED
EDIATYFCQQ
MQLISLTSED
EDIATYFCQQ






SAVYYCASGL
DNTLPYTFGS
SAVYYCASGL
DNTLPYTFGS






TGTGYYWGQG
GTKLELK
TGTGYYWGQG
GTKLELKRTV






TTLTVSS

TTLTVSSAST
AAPSVFIFPP








KGPSVFPLAP
SDEQLKSGTA








SSKSTSGGTA
SVVCLLNNFY








ALGCLVKDYF
PREAKVQWKV








PEPVTVSWNS
DNALQSGNSQ








GALTSGVHTF
ESVTEQDSKD








PAVLQSSGLY
STYSLSSTLT








SLSSVVTVPS
LSKADYEKHK








SSLGTQTYIC
VYACEVTHQG








NVNHKPSNTK
LSSPVTKSFN








VDKKVEPKSC
RGEC








DKTHTCPPCP









APELLGGPSV









FLFPPKPKDT









LMISRTPEVT









CVVVDVSHED









PEVKFNWYVD









GVEVHNAKTK









PREEQYNSTY









RVVSVLTVLH









QDWLNGKEYK









CKVSNKALPA









PIEKTISKAK









GQPREPQVYT









LPPSREEMTK









NQVSLTCLVK









GFYPSDIAVE









WESNGQPENN









YKTTPPVLDS









DGSFFLYSKL









TVDKSRWQQG









NVFSCSVMHE









ALHNHYTQKS









LSLSPGK







 235
 236
 237
 238





8
CD8B247
IgG1
Kappa
EVQLQQSGPE
DIVMTQSPAT
EVQLQQSGPE
DIVMTQSPAT






LVKPGASVKM
LSVTPGERVS
LVKPGASVKM
LSVTPGERVS






SCKASGYTFT
LSCRASQTIS
SCKASGYTFT
LSCRASQTIS






DYYMNWVKQS
HFLHWYQQKS
DYYMNWVKQS
HFLHWYQQKS






HGKSLEWIGR
HESPRLLIKY
HGKSLEWIGR
HESPRLLIKY






VIPNNGGTIY
ASQSISGIPS
VIPNNGGTIY
ASQSISGIPS






NQKFKDKATL
RFSGGGSGSD
NQKFKDKATL
RFSGGGSGSD






TVDKSLSTAY
FILTINSVEP
TVDKSLSTAY
FILTINSVEP






MQLNSLTSED
EDVGMYYCQS
MQLNSLTSED
EDVGMYYCQS






SAVYYCARED
GHSFPYTFGS
SAVYYCARED
GHSFPYTFGS






YSNQGFFLDA
GTKLEIK
YSNQGFFLDA
GTKLEIKRTV






MDYWGQGTSV

MDYWGQGTSV
AAPSVFIFPP






TVSS

TVSSASTKGP
SDEQLKSGTA








SVFPLAPSSK
SVVCLLNNFY








STSGGTAALG
PREAKVQWKV








CLVKDYFPEP
DNALQSGNSQ








VTVSWNSGAL
ESVTEQDSKD








TSGVHTFPAV
STYSLSSTLT








LQSSGLYSLS
LSKADYEKHK








SVVTVPSSSL
VYACEVTHQG








GTQTYICNVN
LSSPVTKSFN








HKPSNTKVDK
RGEC








KVEPKSCDKT









HTCPPCPAPE









LLGGPSVFLF









PPKPKDTLMI









SRTPEVTCVV









VDVSHEDPEV









KFNWYVDGVE









VHNAKTKPRE









EQYNSTYRVV









SVLTVLHQDW









LNGKEYKCKV









SNKALPAPIE









KTISKAKGQP









REPQVYTLPP









SREEMTKNQV









SLTCLVKGFY









PSDIAVEWES









NGQPENNYKT









TPPVLDSDGS









FFLYSKLTVD









KSRWQQGNVF









SCSVMHEALH









NHYTQKSLSL









SPGK







 269
 270
 271
 272





9
CD8B265
IgG1
Kappa
QVQLQQSGPE
DIVMTQSPAT
QVQLQQSGPE
DIVMTQSPAT






LVKPGASVKM
LSVTPGDRVS
LVKPGASVKM
LSVTPGDRVS






SCKASGYSFT
LSCRASQSIS
SCKASGYSFT
LSCRASQSIS






DYYMNWVKQS
HYLHWYQQKS
DYYMNWVKQS
HYLHWYQQKS






HGQSLEWIGR
HESPRLLIKY
HGQSLEWIGR
HESPRLLIKY






VIPRNGATTY
ASQSISGIPS
VIPRNGATTY
ASQSISGIPS






NQNFRGKATL
RFSGSGSGSD
NQNFRGKATL
RFSGSGSGSD






TVDISLRTAY
FTLSINSVEP
TVDISLRTAY
FTLSINSVEP






MHLNSLTSDD
EDVGVYYCQN
MHLNSLTSDD
EDVGVYYCQN






SAVYYCARED
GHSFPYTFGS
SAVYYCARED
GHSFPYTFGS






FSNQGFFLDA
GTKLEMK
FSNQGFFLDA
GTKLEMKRTV






MDYWGQGTSV

MDYWGQGTSV
AAPSVFIFPP






TVSS

TVSSASTKGP
SDEQLKSGTA








SVFPLAPSSK
SVVCLLNNFY








STSGGTAALG
PREAKVQWKV








CLVKDYFPEP
DNALQSGNSQ








VTVSWNSGAL
ESVTEQDSKD








TSGVHTFPAV
STYSLSSTLT








LQSSGLYSLS
LSKADYEKHK








SVVTVPSSSL
VYACEVTHQG








GTQTYICNVN
LSSPVTKSFN








HKPSNTKVDK
RGEC








KVEPKSCDKT









HTCPPCPAPE









LLGGPSVFLF









PPKPKDTLMI









SRTPEVTCVV









VDVSHEDPEV









KFNWYVDGVE









VHNAKTKPRE









EQYNSTYRVV









SVLTVLHQDW









LNGKEYKCKV









SNKALPAPIE









KTISKAKGQP









REPQVYTLPP









SREEMTKNQV









SLTCLVKGFY









PSDIAVEWES









NGQPENNYKT









TPPVLDSDGS









FFLYSKLTVD









KSRWQQGNVF









SCSVMHEALH









NHYTQKSLSL









SPGK







 303
 304
 305
 306





10
CD8B270
IgG1
Kappa
QVQLQQPGAE
DIQMTQTTSS
QVQLQQPGAE
DIQMTQTTSS






LVKPGASVML
LSASLGDRVT
LVKPGASVML
LSASLGDRVT






SCKASGYTFT
ITCRASQDIR
SCKASGYTFT
ITCRASQDIR






NYWMHWVKQR
PYLNWYQQKP
NYWMHWVKQR
PYLNWYQQKP






PGQGLEWIGN
EGTIKLLIYF
PGQGLEWIGN
EGTIKLLIYF






IDPSDSETHY
TSKLHSGVPS
IDPSDSETHY
TSKLHSGVPS






NQKFKDKATL
RFSGSGSGTD
NQKFKDKATL
RFSGSGSGTD






TVDKSSSTAY
YSLTISNLEQ
TVDKSSSTAY
YSLTISNLEQ






MQLSSLTSED
EDIATYFCQQ
MQLSSLTSED
EDIATYFCQQ






SAVYYCASGL
DNTLPYTFGS
SAVYYCASGL
DNTLPYTFGS






TGTGYYWGQG
GTKLELK
TGTGYYWGQG
GTKLELKRTV






TTLTVSS

TTLTVSSAST
AAPSVFIFPP








KGPSVFPLAP
SDEQLKSGTA








SSKSTSGGTA
SVVCLLNNFY








ALGCLVKDYF
PREAKVQWKV








PEPVTVSWNS
DNALQSGNSQ








GALTSGVHTF
ESVTEQDSKD








PAVLQSSGLY
STYSLSSTLT








SLSSVVTVPS
LSKADYEKHK








SSLGTQTYIC
VYACEVTHQG








NVNHKPSNTK
LSSPVTKSFN








VDKKVEPKSC
RGEC








DKTHTCPPCP









APELLGGPSV









FLFPPKPKDT









LMISRTPEVT









CVVVDVSHED









PEVKFNWYVD









GVEVHNAKTK









PREEQYNSTY









RVVSVLTVLH









QDWLNGKEYK









CKVSNKALPA









PIEKTISKAK









GQPREPQVYT









LPPSREEMTK









NQVSLTCLVK









GFYPSDIAVE









WESNGQPENN









YKTTPPVLDS









DGSFFLYSKL









TVDKSRWQQG









NVFSCSVMHE









ALHNHYTQKS









LSLSPGK







 337
 338
 339
 340





11
CD8B213
IgG1
Kappa
EVQLQQSGPE
DIVLTQSQKF
EVQLQQSGPE
DIVLTQSQKF






LVKPGDSMKM
MSTSVGDRVS
LVKPGDSMKM
MSTSVGDRVS






SCKASGYIFT
VTCKASQNVD
SCKASGYIFT
VTCKASQNVD






DYYMDWVKQS
KYVAWYQQKP
DYYMDWVKQS
KYVAWYQQKP






HGKSLEWIGY
GQSPKALIYS
HGKSLEWIGY
GQSPKALIYS






IYPNNGITSY
ASYRYSGVPD
IYPNNGITSY
ASYRYSGVPD






NQKFKGRATL
RFTGSGSGTD
NQKFKGRATL
RFTGSGSGTD






TIDKSSSTAY
FTLTISNVQS
TIDKSSSTAY
FTLTISNVQS






MELHSLTSED
EDLAEYFCQQ
MELHSLTSED
EDLAEYFCQQ






SAVYYCARSI
YNTYPSFGSG
SAVYYCARSI
YNTYPSFGSG






YYDHGGGFPY
TKLEMK
YYDHGGGFPY
TKLEMKRTVA






WGQGTSVTVS

WGQGTSVTVS
APSVFIFPPS






S

SASTKGPSVF
DEQLKSGTAS








PLAPSSKSTS
VVCLLNNFYP








GGTAALGCLV
REAKVQWKVD








KDYFPEPVTV
NALQSGNSQE








SWNSGALTSG
SVTEQDSKDS








VHTFPAVLQS
TYSLSSTLTL








SGLYSLSSVV
SKADYEKHKV








TVPSSSLGTQ
YACEVTHQGL








TYICNVNHKP
SSPVTKSFNR








SNTKVDKKVE
GEC








PKSCDKTHTC









PPCPAPELLG









GPSVFLFPPK









PKDTLMISRT









PEVTCVVVDV









SHEDPEVKFN









WYVDGVEVHN









AKTKPREEQY









NSTYRVVSVL









TVLHQDWLNG









KEYKCKVSNK









ALPAPIEKTI









SKAKGQPREP









QVYTLPPSRE









EMTKNQVSLT









CLVKGFYPSD









IAVEWESNGQ









PENNYKTTPP









VLDSDGSFFL









YSKLTVDKSR









WQQGNVFSCS









VMHEALHNHY









TQKSLSLSPG









K







 371
 372
 373
 374





12
CD8B240
IgG1
Kappa
QVQLQQSGPE
DIVMTQSPAT
QVQLQQSGPE
DIVMTQSPAT






LVKPGTSVKM
LSVTPGDRVS
LVKPGTSVKM
LSVTPGDRVS






SCKASGYTFT
LSCRASQSIS
SCKASGYTFT
LSCRASQSIS






DYYMNWVKQS
DFLHWYQQKS
DYYMNWVKQS
DFLHWYQQKS






HGKSLEWIGR
HESPRLLIKY
HGKSLEWIGR
HESPRLLIKY






VIPSNGGTIY
ASQSISGIPS
VIPSNGGTIY
ASQSISGIPS






NLKFKGKATL
RFSGSGSGSD
NLKFKGKATL
RFSGSGSGSD






TVDKSLSTAY
FTLTINSVEP
TVDKSLSTAY
FTLTINSVEP






MQLNSLTSED
EDVGVYYCQN
MQLNSLTSED
EDVGVYYCQN






SAVYFCARED
GHSFPYTFGS
SAVYFCARED
GHSFPYTFGS






YNNQGFFLDA
GTKLEIK
YNNQGFFLDA
GTKLEIKRTV






MDYWGQGTLV

MDYWGQGTLV
AAPSVFIFPP






TVSA

TVSAASTKGP
SDEQLKSGTA








SVFPLAPSSK
SVVCLLNNFY








STSGGTAALG
PREAKVQWKV








CLVKDYFPEP
DNALQSGNSQ








VTVSWNSGAL
ESVTEQDSKD








TSGVHTFPAV
STYSLSSTLT








LQSSGLYSLS
LSKADYEKHK








SVVTVPSSSL
VYACEVTHQG








GTQTYICNVN
LSSPVTKSFN








HKPSNTKVDK
RGEC








KVEPKSCDKT









HTCPPCPAPE









LLGGPSVFLF









PPKPKDTLMI









SRTPEVTCVV









VDVSHEDPEV









KFNWYVDGVE









VHNAKTKPRE









EQYNSTYRVV









SVLTVLHQDW









LNGKEYKCKV









SNKALPAPIE









KTISKAKGQP









REPQVYTLPP









SREEMTKNQV









SLTCLVKGFY









PSDIAVEWES









NGQPENNYKT









TPPVLDSDGS









FFLYSKLTVD









KSRWQQGNVF









SCSVMHEALH









NHYTQKSLSL









SPGK







 405
 406
 407
 408





13
CD8B36I
IgG1
Kappa
EVQLQQSGPE
DIVMTQSQKF
EVQLQQSGPE
DIVMTQSQKF






LVKPGNSVKM
MSTSVGDRVS
LVKPGNSVKM
MSTSVGDRVS






SCKASGYTFT
VTCKASQNVG
SCKASGYTFT
VTCKASQNVG






DYYMDWVKQS
TYVAWYQQKP
DYYMDWVKQS
TYVAWYQQKP






HGTSLEWIGY
GQSPKALIYS
HGTSLEWIGY
GQSPKALIYS






IYPNNGDTRY
ASYRYSGVPD
IYPNNGDTRY
ASYRYSGVPD






NQKFKDKATL
RFTGSGSGTD
NQKFKDKATL
RFTGSGSGTD






TVDKSSSTAY
FTLTINNVQS
TVDKSSSTAY
FTLTINNVQS






MELHSLTSED
EDLAEYLCQQ
MELHSLTSED
EDLAEYLCQQ






SAVFYCARSI
YNSYPTFGGG
SAVFYCARSI
YNSYPTFGGG






YYDHGGGFPY
TRLEIK
YYDHGGGFPY
TRLEIKRTVA






WGQGTLVTVS

WGQGTLVTVS
APSVFIFPPS






A

AASTKGPSVF
DEQLKSGTAS








PLAPSSKSTS
VVCLLNNFYP








GGTAALGCLV
REAKVQWKVD








KDYFPEPVTV
NALQSGNSQE








SWNSGALTSG
SVTEQDSKDS








VHTFPAVLQS
TYSLSSTLTL








SGLYSLSSVV
SKADYEKHKV








TVPSSSLGTQ
YACEVTHQGL








TYICNVNHKP
SSPVTKSFNR








SNTKVDKKVE
GEC








PKSCDKTHTC









PPCPAPELLG









GPSVFLFPPK









PKDTLMISRT









PEVTCVVVDV









SHEDPEVKFN









WYVDGVEVHN









AKTKPREEQY









NSTYRVVSVL









TVLHQDWLNG









KEYKCKVSNK









ALPAPIEKTI









SKAKGQPREP









QVYTLPPSRE









EMTKNQVSLT









CLVKGFYPSD









IAVEWESNGQ









PENNYKTTPP









VLDSDGSFFL









YSKLTVDKSR









WQQGNVFSCS









VMHEALHNHY









TQKSLSLSPG









K







 439
 440
 441
 442





14
CD8B246
IgG1
Kappa
QVQLKESGPG
DIQMTQTTSS
QVQLKESGPG
DIQMTQTTSS






ILKPSQTLSL
LSASLGDRVT
ILKPSQTLSL
LSASLGDRVT






TCSFSGFSLS
ISCRASQDIR
TCSFSGFSLS
ISCRASQDIR






TSGMNVGWIR
NYLNWYQQKP
TSGMNVGWIR
NYLNWYQQKP






QPSGKGLEWL
DGTVKLLIYH
QPSGKGLEWL
DGTVKLLIYH






AHIWWDDDKY
TSRLHSGVPS
AHIWWDDDKY
TSRLHSGVPS






YNPSLKSQLT
RFSGSGSGTD
YNPSLKSQLT
RFSGSGSGTD






ISKDTSRNQV
YSLTISNLEQ
ISKDTSRNQV
YSLTISNLEQ






FLKITSVDTA
EDIATYFCQQ
FLKITSVDTA
EDIATYFCQQ






DTATYYCARR
GNTLPWTFGA
DTATYYCARR
GNTLPWTFGA






GNYGNYEFAY
GTKLELK
GNYGNYEFAY
GTKLELKRTV






WGQGTTLTVS

WGQGTTLTVS
AAPSVFIFPP






S

SASTKGPSVF
SDEQLKSGTA








PLAPSSKSTS
SVVCLLNNFY








GGTAALGCLV
PREAKVQWKV








KDYFPEPVTV
DNALQSGNSQ








SWNSGALTSG
ESVTEQDSKD








VHTFPAVLQS
STYSLSSTLT








SGLYSLSSVV
LSKADYEKHK








TVPSSSLGTQ
VYACEVTHQG








TYICNVNHKP
LSSPVTKSFN








SNTKVDKKVE
RGEC








PKSCDKTHTC









PPCPAPELLG









GPSVFLFPPK









PKDTLMISRT









PEVTCVVVDV









SHEDPEVKFN









WYVDGVEVHN









AKTKPREEQY









NSTYRVVSVL









TVLHQDWLNG









KEYKCKVSNK









ALPAPIEKTI









SKAKGQPREP









QVYTLPPSRE









EMTKNQVSLT









CLVKGFYPSD









IAVEWESNGQ









PENNYKTTPP









VLDSDGSFFL









YSKLTVDKSR









WQQGNVFSCS









VMHEALHNHY









TQKSLSLSPG









K







 473
 474
 475
 476





15
CD8B268
IgG1
Kappa
QVQLQQSGAE
DIQMTQSPAS
QVQLQQSGAE
DIQMTQSPAS






LVKPGASVKL
LSASVGQTVT
LVKPGASVKL
LSASVGQTVT






SCKASGYTFT
ITCRASGNIH
SCKASGYTFT
ITCRASGNIH






VYTIHWVKQR
NYLAWFQQKQ
VYTIHWVKQR
NYLAWFQQKQ






SGQGLEWIGW
GKSPQLLVYN
SGQGLEWIGW
GKSPQLLVYN






FYPGSGNIKY
AKTLADGVPS
FYPGSGNIKY
AKTLADGVPS






NEKFKDKATL
RFSGSGSGTQ
NEKFKDKATL
RFSGSGSGTQ






TADKSSHTVY
YSLKINSLQT
TADKSSHTVY
YSLKINSLQT






MELSRLTSED
EDFGNYYCQH
MELSRLTSED
EDFGNYYCQH






SAVYFCARHE
FWNTPYTFGG
SAVYFCARHE
FWNTPYTFGG






DNHYYDGNSW
GTKLEIK
DNHYYDGNSW
GTKLEIKRTV






FAYWGQGTLV

FAYWGQGTLV
AAPSVFIFPP






TVSA

TVSAASTKGP
SDEQLKSGTA








SVFPLAPSSK
SVVCLLNNFY








STSGGTAALG
PREAKVQWKV








CLVKDYFPEP
DNALQSGNSQ








VTVSWNSGAL
ESVTEQDSKD








TSGVHTFPAV
STYSLSSTLT








LQSSGLYSLS
LSKADYEKHK








SVVTVPSSSL
VYACEVTHQG








GTQTYICNVN
LSSPVTKSFN








HKPSNTKVDK
RGEC








KVEPKSCDKT









HTCPPCPAPE









LLGGPSVFLF









PPKPKDTLMI









SRTPEVTCVV









VDVSHEDPEV









KFNWYVDGVE









VHNAKTKPRE









EQYNSTYRVV









SVLTVLHQDW









LNGKEYKCKV









SNKALPAPIE









KTISKAKGQP









REPQVYTLPP









SREEMTKNQV









SLTCLVKGFY









PSDIAVEWES









NGQPENNYKT









TPPVLDSDGS









FFLYSKLTVD









KSRWQQGNVF









SCSVMHEALH









NHYTQKSLSL









SPGK







 507
 508
 509
 510





16
CD8B271
IgG1
Kappa
DVQLQESGPG
DIQMTQTTSS
DVQLQESGPG
DIQMTQTTSS






LVAPSQSLSI
LSASLGDRVT
LVAPSQSLSI
LSASLGDRVT






TCTVSGFSLS
ISCSASQGIS
TCTVSGFSLS
ISCSASQGIS






IYSIHWVRQP
NYLNWYQQKP
IYSIHWVRQP
NYLNWYQQKP






PGKGLEWLGM
DGTVKLLIYD
PGKGLEWLGM
DGTVKLLIYD






IWGGGDTDYN
TSILYSGVPS
IWGGGDTDYN
TSILYSGVPS






SALKSRLSIS
RFSGSGSGTD
SALKSRLSIS
RFSGSGSGTD






KDNSESQVFL
YSLTISNLEP
KDNSESQVFL
YSLTISNLEP






KMNSLQTDDT
EDVATYYCQQ
KMNSLQTDDT
EDVATYYCQQ






AMYYCARNPH
YSNLPYTFGS
AMYYCARNPH
YSNLPYTFGS






YYGGTYEYFD
GTKLEIK
YYGGTYEYFD
GTKLEIKRTV






VWGTGTTVTV

VWGTGTTVTV
AAPSVFIFPP






SS

SSASTKGPSV
SDEQLKSGTA








FPLAPSSKST
SVVCLLNNFY








SGGTAALGCL
PREAKVQWKV








VKDYFPEPVT
DNALQSGNSQ








VSWNSGALTS
ESVTEQDSKD








GVHTFPAVLQ
STYSLSSTLT








SSGLYSLSSV
LSKADYEKHK








VTVPSSSLGT
VYACEVTHQG








QTYICNVNHK
LSSPVTKSFN








PSNTKVDKKV
RGEC








EPKSCDKTHT









CPPCPAPELL









GGPSVFLFPP









KPKDTLMISR









TPEVTCVVVD









VSHEDPEVKF









NWYVDGVEVH









NAKTKPREEQ









YNSTYRVVSV









LTVLHQDWLN









GKEYKCKVSN









KALPAPIEKT









ISKAKGQPRE









PQVYTLPPSR









EEMTKNQVSL









TCLVKGFYPS









DIAVEWESNG









QPENNYKTTP









PVLDSDGSFF









LYSKLTVDKS









RWQQGNVFSC









SVMHEALHNH









YTQKSLSLSP









GK







 541
 542
 543
 544





17
CD8B273
IgG1
Kappa
QVQLQQSGAE
DIQMTQSPAS
QVQLQQSGAE
DIQMTQSPAS






LVKPGASVKL
LSASVGETVT
LVKPGASVKL
LSASVGETVT






SCKASGYTFT
ITCRASGNIH
SCKASGYTFT
ITCRASGNIH






EYTIHWVKQR
NYLAWFQQKQ
EYTIHWVKQR
NYLAWFQQKQ






SGQGLEWIGW
GKSPQLLVYN
SGQGLEWIGW
GKSPQLLVYN






FYPGTGSIKY
AKTLADGVPS
FYPGTGSIKY
AKTLADGVPS






NEKFKDKATL
RFSGSGSGTQ
NEKFKDKATL
RFSGSGSGTQ






TADKSSHTVY
YSLKINSLQA
TADKSSHTVY
YSLKINSLQA






MELSKLTSED
EDFGSYYCQH
MELSKLTSED
EDFGSYYCQH






SAVYFCARHE
FWSTPYTFGS
SAVYFCARHE
FWSTPYTFGS






DNHYYDGNSW
GTKLEIK
DNHYYDGNSW
GTKLEIKRTV






FAYWGQGTLV

FAYWGQGTLV
AAPSVFIFPP






TVSA

TVSAASTKGP
SDEQLKSGTA








SVFPLAPSSK
SVVCLLNNFY








STSGGTAALG
PREAKVQWKV








CLVKDYFPEP
DNALQSGNSQ








VTVSWNSGAL
ESVTEQDSKD








TSGVHTFPAV
STYSLSSTLT








LQSSGLYSLS
LSKADYEKHK








SVVTVPSSSL
VYACEVTHQG








GTQTYICNVN
LSSPVTKSFN








HKPSNTKVDK
RGEC








KVEPKSCDKT









HTCPPCPAPE









LLGGPSVFLF









PPKPKDTLMI









SRTPEVTCVV









VDVSHEDPEV









KFNWYVDGVE









VHNAKTKPRE









EQYNSTYRVV









SVLTVLHQDW









LNGKEYKCKV









SNKALPAPIE









KTISKAKGQP









REPQVYTLPP









SREEMTKNQV









SLTCLVKGFY









PSDIAVEWES









NGQPENNYKT









TPPVLDSDGS









FFLYSKLTVD









KSRWQQGNVF









SCSVMHEALH









NHYTQKSLSL









SPGK







 575
 576
 577
 578





18
CD8B288
IgG1
Kappa
QVQLQQSGAE
DIQMTQSPAS
QVQLQQSGAE
DIQMTQSPAS






LVKPGASVKL
LSASVGDTVT
LVKPGASVKL
LSASVGDTVT






SCKASGYTFT
ITCRASGNIH
SCKASGYTFT
ITCRASGNIH






EYTIHWVKQK
NYLAWFQQKQ
EYTIHWVKQK
NYLAWFQQKQ






SGQGLEWIGW
GKSPQLLVYN
SGQGLEWIGW
GKSPQLLVYN






FYPGNGNMRY
AKTLADGVPS
FYPGNGNMRY
AKTLADGVPS






NEKFKDKATL
RFSGSGSGTQ
NEKFKDKATL
RFSGSGSGTQ






TADRSSHTVY
FSLKINSLQP
TADRSSHTVY
FSLKINSLQP






MELSRLTSED
EDFGTYYCQH
MELSRLTSED
EDFGTYYCQH






SAVYFCARYE
FWSTPFTFGS
SAVYFCARYE
FWSTPFTFGS






DNHYYDGASW
GTKLEMK
DNHYYDGASW
GTKLEMKRTV






FAYWGQGTSV

FAYWGQGTSV
AAPSVFIFPP






TVSS

TVSSASTKGP
SDEQLKSGTA








SVFPLAPSSK
SVVCLLNNFY








STSGGTAALG
PREAKVQWKV








CLVKDYFPEP
DNALQSGNSQ








VTVSWNSGAL
ESVTEQDSKD








TSGVHTFPAV
STYSLSSTLT








LQSSGLYSLS
LSKADYEKHK








SVVTVPSSSL
VYACEVTHQG








GTQTYICNVN
LSSPVTKSFN








HKPSNTKVDK
RGEC








KVEPKSCDKT









HTCPPCPAPE









LLGGPSVFLF









PPKPKDTLMI









SRTPEVTCVV









VDVSHEDPEV









KFNWYVDGVE









VHNAKTKPRE









EQYNSTYRVV









SVLTVLHQDW









LNGKEYKCKV









SNKALPAPIE









KTISKAKGQP









REPQVYTLPP









SREEMTKNQV









SLTCLVKGFY









PSDIAVEWES









NGQPENNYKT









TPPVLDSDGS









FFLYSKLTVD









KSRWQQGNVF









SCSVMHEALH









NHYTQKSLSL









SPGK







 609
 610
 611
 612





19
CD8B292
IgG1
Kappa
QVQLQQPGAE
QIVLTQSPAI
QVQLQQPGAE
QIVLTQSPAI






LVKPGASVKL
MSASLGERVT
LVKPGASVKL
MSASLGERVT






SCTGSGFNFK
LTCTASSSVS
SCTGSGFNFK
LTCTASSSVS






DDYIYWVKQR
SSYLHWYQQK
DDYIYWVKQR
SSYLHWYQQK






PEQGLEWIGW
PGSSPKLWIY
PEQGLEWIGW
PGSSPKLWIY






IDPENGATEY
STSNLASGVP
IDPENGATEY
STSNLASGVP






ASKFQGKATI
ARFSGSGSGT
ASKFQGKATI
ARFSGSGSGT






TADTSSNIAY
SYSLTISNME
TADTSSNIAY
SYSLTISNME






LQLSSLTSED
AEDAATYYCH
LQLSSLTSED
AEDAATYYCH






TAVYYCSLHD
QYHRSPLTFG
TAVYYCSLHD
QYHRSPLTFG






YGYAMDYWGQ
GGTKLEIK
YGYAMDYWGQ
GGTKLEIKRT






GTSVTVSS

GTSVTVSSAS
VAAPSVFIFP








TKGPSVFPLA
PSDEQLKSGT








PSSKSTSGGT
ASVVCLLNNF








AALGCLVKDY
YPREAKVQWK








FPEPVTVSWN
VDNALQSGNS








SGALTSGVHT
QESVTEQDSK








FPAVLQSSGL
DSTYSLSSTL








YSLSSVVTVP
TLSKADYEKH








SSSLGTQTYI
KVYACEVTHQ








CNVNHKPSNT
GLSSPVTKSF








KVDKKVEPKS
NRGEC








CDKTHTCPPC









PAPELLGGPS









VFLFPPKPKD









TLMISRTPEV









TCVVVDVSHE









DPEVKFNWYV









DGVEVHNAKT









KPREEQYNST









YRVVSVLTVL









HQDWLNGKEY









KCKVSNKALP









APIEKTISKA









KGQPREPQVY









TLPPSREEMT









KNQVSLTCLV









KGFYPSDIAV









EWESNGQPEN









NYKTTPPVLD









SDGSFFLYSK









LTVDKSRWQQ









GNVFSCSVMH









EALHNHYTQK









SLSLSPGK







 643
 644
 645
 646





20
CD8B303
IgG1
Kappa
QVQLKESGPG
DVQMIQSPSS
QVQLKESGPG
DVQMIQSPSS






LVAPSQSLSI
LSASLGGTVT
LVAPSQSLSI
LSASLGGTVT






TCTVSGFSLS
ITCKASQDIK
TCTVSGFSLS
ITCKASQDIK






IYSIHWVRQP
KYMAWYQHKP
IYSIHWVRQP
KYMAWYQHKP






PGKGLEWLGM
GKGPRLLIHY
PGKGLEWLGM
GKGPRLLIHY






IWGGGSTDYN
TSSLQPGIPS
IWGGGSTDYN
TSSLQPGIPS






STLNSRLSII
RFSGSGSGRD
STLNSRLSII
RFSGSGSGRD






KDNSKSQVFL
YYFSISNLEP
KDNSKSQVFL
YYFSISNLEP






KMNSLQTDDT
EDIATYFCLQ
KMNSLQTDDT
EDIATYFCLQ






AMYYCARNPH
YDNLFTFGSG
AMYYCARNPH
YDNLFTFGSG






HYGGSTGAMD
TKLELK
HYGGSTGAMD
TKLELKRTVA






YWGQGTTVTV

YWGQGTTVTV
APSVFIFPPS






SS

SSASTKGPSV
DEQLKSGTAS








FPLAPSSKST
VVCLLNNFYP








SGGTAALGCL
REAKVQWKVD








VKDYFPEPVT
NALQSGNSQE








VSWNSGALTS
SVTEQDSKDS








GVHTFPAVLQ
TYSLSSTLTL








SSGLYSLSSV
SKADYEKHKV








VTVPSSSLGT
YACEVTHQGL








QTYICNVNHK
SSPVTKSFNR








PSNTKVDKKV
GEC








EPKSCDKTHT









CPPCPAPELL









GGPSVFLFPP









KPKDTLMISR









TPEVTCVVVD









VSHEDPEVKF









NWYVDGVEVH









NAKTKPREEQ









YNSTYRVVSV









LTVLHQDWLN









GKEYKCKVSN









KALPAPIEKT









ISKAKGQPRE









PQVYTLPPSR









EEMTKNQVSL









TCLVKGFYPS









DIAVEWESNG









QPENNYKTTP









PVLDSDGSFF









LYSKLTVDKS









RWQQGNVFSC









SVMHEALHNH









YTQKSLSLSP









GK







 677
 678
 679
 680





21
CD8B304
IgG1
Kappa
QVTLKESGPG
DIQMTQTTSS
QVTLKESGPG
DIQMTQTTSS






ILKPSQTLSL
LSASLGDRVT
ILKPSQTLSL
LSASLGDRVT






TCSFSGFSLS
ISCRASQDIR
TCSFSGFSLS
ISCRASQDIR






TSGMNVGWIR
NYLNWYQQKP
TSGMNVGWIR
NYLNWYQQKP






QPSGKGLEWL
DGTVKLLIYH
QPSGKGLEWL
DGTVKLLIYH






AHIWWDDDKY
TSRLHSGVPS
AHIWWDDDKY
TSRLHSGVPS






YNPSLKSQLT
RFSGSGSGTD
YNPSLKSQLT
RFSGSGSGTD






ISKDTSRNQV
YSLTISNLDQ
ISKDTSRNQV
YSLTISNLDQ






FLKITSVDTA
EDIATYFCQQ
FLKITSVDTA
EDIATYFCQQ






DTATYYCARR
GNTLPWTFGA
DTATYYCARR
GNTLPWTFGA






GNYGNYEFAY
GTKLELK
GNYGNYEFAY
GTKLELKRTV






WGQGTTVTVS

WGQGTTVTVS
AAPSVFIFPP






S

SASTKGPSVF
SDEQLKSGTA








PLAPSSKSTS
SVVCLLNNFY








GGTAALGCLV
PREAKVQWKV








KDYFPEPVTV
DNALQSGNSQ








SWNSGALTSG
ESVTEQDSKD








VHTFPAVLQS
STYSLSSTLT








SGLYSLSSVV
LSKADYEKHK








TVPSSSLGTQ
VYACEVTHQG








TYICNVNHKP
LSSPVTKSFN








SNTKVDKKVE
RGEC








PKSCDKTHTC









PPCPAPELLG









GPSVFLFPPK









PKDTLMISRT









PEVTCVVVDV









SHEDPEVKFN









WYVDGVEVHN









AKTKPREEQY









NSTYRVVSVL









TVLHQDWLNG









KEYKCKVSNK









ALPAPIEKTI









SKAKGQPREP









QVYTLPPSRE









EMTKNQVSLT









CLVKGFYPSD









IAVEWESNGQ









PENNYKTTPP









VLDSDGSFFL









YSKLTVDKSR









WQQGNVFSCS









VMHEALHNHY









TQKSLSLSPG









K







 711
 712
 713
 714





22
CD8B312
IgG1
Kappa
QVQLQQPGAD
DIVLTQSPAT
QVQLQQPGAD
DIVLTQSPAT






LVKPGASVKL
LSVTPGDSVS
LVKPGASVKL
LSVTPGDSVS






SCKASGYTFT
LSCRASQSIN
SCKASGYTFT
LSCRASQSIN






SFWMHWVKQR
NNLHWYQQKS
SFWMHWVKQR
NNLHWYQQKS






PGQGLEWIGN
HESPRLLIKY
PGQGLEWIGN
HESPRLLIKY






VDPSDSQTHY
TSQSISGIPS
VDPSDSQTHY
TSQSISGIPS






NQKFKDKATL
RFSGSGSGPD
NQKFKDKATL
RFSGSGSGPD






TVDKSSNTAY
FTLSINSVET
TVDKSSNTAY
FTLSINSVET






MQLSSLTSED
EDFGMYFCQQ
MQLSSLTSED
EDFGMYFCQQ






SAVYYCARST
SNSWPLTFGG
SAVYYCARST
SNSWPLTFGG






YYRYDGPFTY
GTKLEIK
YYRYDGPFTY
GTKLEIKRTV






WGQGTTVTVS

WGQGTTVTVS
AAPSVFIFPP






S

SASTKGPSVF
SDEQLKSGTA








PLAPSSKSTS
SVVCLLNNFY








GGTAALGCLV
PREAKVQWKV








KDYFPEPVTV
DNALQSGNSQ








SWNSGALTSG
ESVTEQDSKD








VHTFPAVLQS
STYSLSSTLT








SGLYSLSSVV
LSKADYEKHK








TVPSSSLGTQ
VYACEVTHQG








TYICNVNHKP
LSSPVTKSFN








SNTKVDKKVE
RGEC








PKSCDKTHTC









PPCPAPELLG









GPSVFLFPPK









PKDTLMISRT









PEVTCVVVDV









SHEDPEVKFN









WYVDGVEVHN









AKTKPREEQY









NSTYRVVSVL









TVLHQDWLNG









KEYKCKVSNK









ALPAPIEKTI









SKAKGQPREP









QVYTLPPSRE









EMTKNQVSLT









CLVKGFYPSD









IAVEWESNGQ









PENNYKTTPP









VLDSDGSFFL









YSKLTVDKSR









WQQGNVFSCS









VMHEALHNHY









TQKSLSLSPG









K







 745
 746
 747
 748





23
CD8B347
IgG1
Kappa
QVQLQQPGAE
DIQMTQSPAS
QVQLQQPGAE
DIQMTQSPAS






LAKPGTSVKM
LSASVGETVT
LAKPGTSVKM
LSASVGETVT






SCKASGYTFT
ITCRASGNIH
SCKASGYTFT
ITCRASGNIH






SYWMNWIKQR
NYLAWYQQKQ
SYWMNWIKQR
NYLAWYQQKQ






PGQGLEWIGA
GKSPQLLVFN
PGQGLEWIGA
GKSPQLLVFN






VNPSNSYTEY
AETLADGVPS
VNPSNSYTEY
AETLADGVPS






AQKFKDKAIL
RFSGSGSGTQ
AQKFKDKAIL
RFSGSGSGTQ






TADKSSSTAY
FSLKINSLQP
TADKSSSTAY
FSLKINSLQP






MSLSGLTSEA
EDFGTYYCQH
MSLSGLTSEA
EDFGTYYCQH






SAVYYCARSG
FWNNPLTLGA
SAVYYCARSG
FWNNPLTLGA






LYNTNHLAWF
GTKLELK
LYNTNHLAWF
GTKLELKRTV






AYWGQGTLVT

AYWGQGTLVT
AAPSVFIFPP






VSA

VSAASTKGPS
SDEQLKSGTA








VFPLAPSSKS
SWCLLNNFYP








TSGGTAALGC
REAKVQWKVD








LVKDYFPEPV
NALQSGNSQE








TVSWNSGALT
SVTEQDSKDS








SGVHTFPAVL
TYSLSSTLTL








QSSGLYSLSS
SKADYEKHKV








WTVPSSSLGT
YACEVTHQGL








QTYICNVNHK
SSPVTKSFNR








PSNTKVDKKV
GEC








EPKSCDKTHT









CPPCPAPELL









GGPSVFLFPP









KPKDTLMISR









TPEVTCVWDV









SHEDPEVKFN









WYVDGVEVHN









AKTKPREEQY









NSTYRWSVLT









VLHQDWLNGK









EYKCKVSNKA









LPAPIEKTIS









KAKGQPREPQ









VYTLPPSREE









MTKNQVSLTC









LVKGFYPSDI









AVEWESNGQP









ENNYKTTPPV









LDSDGSFFLY









SKLTVDKSRW









QQGNVFSCSV









MHEALHNHYT









QKSLSLSPGK







 779
 780
 781
 782





24
CD8B350
IgG1
Kappa
EVQLQQSGAE
DIVMTQSPAS
EVQLQQSGAE
DIVMTQSPAS






LAKPGTSVKM
LSASVGETVT
LAKPGTSVKM
LSASVGETVT






SCKASGYTFA
ITCRASGNIH
SCKASGYTFA
ITCRASGNIH






AYWINWLKQR
NYLAWYQQKQ
AYWINWLKQR
NYLAWYQQKQ






PGQGLEWIGS
GKSPQVLVYN
PGQGLEWIGS
GKSPQVLVYN






INPSNGYTEY
AETLADSVPS
INPSNGYTEY
AETLADSVPS






SQKFKDKAIL
RFSGSGSGTQ
SQKFKDKAIL
RFSGSGSGTQ






TADKSSSTAY
FSLKINSLQP
TADKSSSTAY
FSLKINSLQP






MQLSSLTSED
EDFGNYYCQH
MQLSSLTSED
EDFGNYYCQH






SAVYYCSRSG
FWNSPLTFGG
SAVYYCSRSG
FWNSPLTFGG






LYYTNHLAWC
GTKLEIK
LYYTNHLAWC
GTKLEIKRTV






PYVJGQGTTV

PYWGQGTTVT
AAPSVFIFPP






TVSS

VSSASTKGPS
SDEQLKSGTA








VFPLAPSSKS
SWCLLNNFYP








TSGGTAALGC
REAKVQWKVD








LVKDYFPEPV
NALQSGNSQE








TVSWNSGALT
SVTEQDSKDS








SGVHTFPAVL
TYSLSSTLTL








QSSGLYSLSS
SKADYEKHKV








WTVPSSSLGT
YACEVTHQGL








QTYICNVNHK
SSPVTKSFNR








PSNTKVDKKV
GEC








EPKSCDKTHT









CPPCPAPELL









GGPSVFLFPP









KPKDTLMISR









TPEVTCVWDV









SHEDPEVKFN









WYVDGVEVHN









AKTKPREEQY









NSTYRWSVLT









VLHQDWLNGK









EYKCKVSNKA









LPAPIEKTIS









KAKGQPREPQ









VYTLPPSREE









MTKNQVSLTC









LVKGFYPSDI









AVEWESNGQP









ENNYKTTPPV









LDSDGSFFLY









SKLTVDKSRW









QQGNVFSCSV









MHEALHNHYT









QKSLSLSPGK







 813
 814
 815
 816





25
CD8B356
IgG1
Kappa
DVQLQESGPG
DIVLTQSQKF
DVQLQESGPG
DIVLTQSQKF






LVKPSQSLSL
MSTTVGDRVS
LVKPSQSLSL
MSTTVGDRVS






TCSVTGYSIT
ITCKASQNVG
TCSVTGYSIT
ITCKASQNVG






SGYYWNWIRQ
TAVAWYQQKP
SGYYWNWIRQ
TAVAWYQQKP






FPGNKLEWMG
GQSPKLLIYS
FPGNKLEWMG
GQSPKLLIYS






YISYDGSNNY
ASYRYTGVPD
YISYDGSNNY
ASYRYTGVPD






NPSLKNRISI
RFTGSGSGTH
NPSLKNRISI
RFTGSGSGTH






TRDTSKNQFF
FTLTISNMQS
TRDTSKNQFF
FTLTISNMQS






LKLNSVTTED
EDLADYFCQQ
LKLNSVTTED
EDLADYFCQQ






TATYYCVRN
YSSYLTFGSG
TATYYCVRNH
YSSYLTFGSG






HGDAMDYWGQ
TKLEIK
GDAMDYWGQG
TKLEIKRTVA






GTSVTVSS

TSVTVSSAST
APSVFIFPPS








KGPSVFPLAP
DEQLKSGTAS








SSKSTSGGTA
WCLLNNFYPR








ALGCLVKDYF
EAKVQWKVDN








PEPVTVSWNS
ALQSGNSQES








GALTSGVHTF
VTEQDSKDST








PAVLQSSGLY
YSLSSTLTL








SLSSVVTVPS
SKADYEKHKV








SSLGTQTYIC
YACEVTHQGL








NVNHKPSNTK
SSPVTKSFNR








VDKKVEPKSC
GEC








DKTHTCPPCP









APELLGGPSV









FLFPPKPKDT









LMISRTPEVT









CVWDVSHEDP









EVKFNWYVDG









VEVHNAKTKP









REEQYNSTYR









WSVLTVLHQD









WLNGKEYKCK









VSNKALPAPI









EKTISKAKGQ









PREPQVYTLP









PSREEMTKNQ









VSLTCLVK









GFYPSDIAVE









WESNGQPENN









YKTTPPVLDS









DGSFFLYSKL









TVDKSRWQQG









NVFSCSVMHE









ALHNHYTQKS









LSLSPGK







 847
 848
 849
 850





26
CD8B369
IgG1
Kappa
QVQLQQSGAE
DIVMTQSPAS
QVQLQQSGAE
DIVMTQSPAS






LVKPGASVKL
LSASVGETVT
LVKPGASVKL
LSASVGETVT






SCKTSGFTFT
ITCRASENIY
SCKTSGFTFT
ITCRASENIY






NTYISWLKQK
SYLAWYQQKQ
NTYISWLKQK
SYLAWYQQKQ






PRQSLEWIAW
GKSPQLLVYY
PRQSLEWIAW
GKSPQLLVYY






IYTGTGGTWY
AKTLTDGVPS
IYTGTGGTWY
AKTLTDGVPS






NQKFTDKAQL
RFSGSGSGTQ
NQKFTDKAQL
RFSGSGSGTQ






TVDTSSSTAY
FSLKINSLQP
TVDTSSSTAY
FSLKINSLQP






MQVSSLTSED
EDFGSYYCQH
MQVSSLTSED
EDFGSYYCQH






SAIYYCARTN
HYGRPYTFGS
SAIYYCARTN
HYGRPYTFGS






WDWYFDVWGA
GTKLEIK
WDWYFDVWGA
GTKLEIKRTV






GTSVTVSS

GTSVTVSSAS
AAPSVFIFPP








TKGPSVFPLA
SDEQLKSGTA








PSSKSTSGGT
SWCLLNNFYP








AALGCLVKDY
REAKVQWKVD








FPEPVTVSWN
NALQSGNSQE








SGALTSGVHT
SVTEQDSKDS








FPAVLQSSGL
TYSLSSTLTL








YSLSSWTVPS
SKADYEKHKV








SSLGTQTYIC
YACEVTHQGL








NVNHKPSNTK
SSPVTKSFNR








VDKKVEPKSC
GEC








DKTHTCPPCP









APELLGGPSV









FLFPPKPKDT









LMISRTPEVT









CVWDVSHEDP









EVKFNWYVDG









VEVHNAKTKP









REEQYNSTYR









WSVLTVLHQD









WLNGKEYKCK









VSNKALPAPI









EKTISKAKGQ









PREPQVYTLP









PSREEMTKNQ









VSLTCLVKGF









YPSDIAVEWE









SNGQPENNYK









TTPPVLDSDG









SFFLYSKLTV









DKSRWQQGNV









FSCSVMHEAL









HNHYTQKSLS









LSPGK







 881
 882
 883
 884





27
CD8B371
IgG1
Kappa
EVKLVESGGG
NTQMNQTPSS
EVKLVESGGG
NTQMNQTPSS






LVQPGSSMKL
LSASLGDTIT
LVQPGSSMKL
LSASLGDTIT






SCTASGFTFS
ITCHASQNIN
SCTASGFTFS
ITCHASQNIN






DYYMAWVRQV
VWLSWYQQKP
DYYMAWVRQV
VWLSWYQQKP






PEKGLEWVAH
GNIPKLLIYK
PEKGLEWVAH
GNIPKLLIYK






INYDGSITYY
ASNLHTGVPS
INYDGSITYY
ASNLHTGVPS






LDSLKSRFII
RFSGSGSGTG
LDSLKSRFII
RFSGSGSGTG






SRDNAKNILY
FTLTISSLQP
SRDNAKNILY
FTLTISSLQP






LQMSSLKSED
EDIATYYCQQ
LQMSSLKSED
EDIATYYCQQ






TATYYCARED
GQSYPLTFGS
TATYYCARED
GQSYPLTFGS






YSNYGFAYWG
GTKLEMK
YSNYGFAYWG
GTKLEMKRTV






QGTLVTVSA

QGTLVTVSAA
AAPSVFIFPP








STKGPSVFPL
SDEQLKSGTA








APSSKSTSGG
SWCLLNNFYP








TAALGCLVKD
REAKVQWKVD








YFPEPVTVSW
NALQSGNSQE








NSGALTSGVH
SVTEQDSKDS








TFPAVLQSSG
TYSLSSTLTL








LYSLSSWTVP
SKADYEKHKV








SSSLGTQTYI
YACEVTHQGL








CNVNHKPSNT
SSPVTKSFNR








KVDKKVEPKS
GEC








CDKTHTCPPC









PAPELLGGPS









VFLFPPKPKD









TLMISRTPEV









TCWVDVSHED









PEVKFNWYVD









GVEVHNAKTK









PREEQYNSTY









RWSVLTVLHQ









DWLNGKEYKC









KVSNKALPAP









IEKTISKAKG









QPREPQVYTL









PPSREEMTKN









QVSLTCLVKG









FYPSDIAVEW









ESNGQPENNY









KTTPPVLDSD









GSFFLYSKLT









VDKSRWQQGN









VFSCSVMHEA









LHNHYTQKSL









SLSPGK







 915
 916
 917
 918





28
CD8B182
IgG1
Kappa
EVQLQQSGAA
DIKMTQSPAS
EVQLQQSGAA
DIKMTQSPAS






LAKPGTSVKM
LSASVGETVT
LAKPGTSVKM
LSASVGETVT






SCKASGYTFT
ITCRASENIH
SCKASGYTFT
ITCRASENIH






SYWMNWVRQR
NYLAWYQQIQ
SYWMNWVRQR
NYLAWYQQIQ






PGQGLEWIGA
GKSPQLLVYN
PGQGLEWIGA
GKSPQLLVYN






VNPTNYYTEY
AKTLANGVPS
VNPTNYYTEY
AKTLANGVPS






IQKFKDKAIL
RFSGSASGTQ
IQKFKDKAIL
RFSGSASGTQ






TADKSSS
FSLTINSLQP
TADKSSSTAY
FSLTINSLQP






TAYMHLSGLT
EDFGSYYCQH
MHLSGLTSED
EDFGSYYCQH






SEDSAVYYCA
FWTTPLTFGA
SAVYYCARSG
FWTTPLTFGA






RSGLYNTNHL
GTKLELK
LYNTNHLAWF
GTKLELKRTV






AWFAYWGQGT

AYWGQGTTVT
AAPSVFIFPP






TVTVSS

VSSASTKGPS
SDEQLKSGTA








VFPLAPSSKS
SVVCLLNNFY








TSGGTAALGC
PREAKVQWKV








LVKDYFPEPV
DNALQSGNSQ








TVSWNSGALT
ESVTEQDSKD








SGVHTFPAVL
STYSLSSTLT








QSSGLYSLSS
LSKADYEKHK








VVTVPSSSLG
VYACEVTHQG








TQTYICNVNH
LSSPVTKSFN








KPSNTKVDKK
RGEC








VEPKSCDKTH









TCPPCPAPEL









LGGPSVFLFP









PKPKDTLMI









SRTPEVTCVV









VDVSHEDPEV









KFNWYVDGVE









VHNAKTKPRE









EQYNSTYRVV









SVLTVLHQDW









LNGKEYKCKV









SNKALPAPIE









KTISKAKGQP









REPQVYTLPP









SREEMTKNQV









SLTCLVKGFY









PSDIAVEWES









NGQPENNYKT









TPPVLDSDGS









FFLYSKLTVD









KSRWQQGNVF









SCSVMHEALH









NHYTQKSLSL









SPGK







 949
 950
 951
 952





29
CD8B205
IgG1
Kappa
QVQLQQPGAE
DIQMTQSPAS
QVQLQQPGAE
DIQMTQSPAS






LVKPGASVKL
LSASVGETVT
LVKPGASVKL
LSASVGETVT






SCKASGYSFN
ITCRASENIY
SCKASGYSFN
ITCRASENIY






SYWMHWVKQR
SYLAWYQQKQ
SYWMHWVKQR
SYLAWYQQKQ






PGQGLEWIGN
GKSPQLLVYN
PGQGLEWIGN
GKSPQLLVYN






IDPSDSETHY
AKTLAEGVPS
IDPSDSETHY
AKTLAEGVPS






NQKFKDKATL
RFSGSGSGTQ
NQKFKDKATL
RFSGSGSGTQ






TVDKSSSTAY
FSLKINSLQP
TVDKSSSTAY
FSLKINSLQP






MQLSSLTSED
EDFGSYYCQH
MQLSSLTSED
EDFGSYYCQH






SAVYYCARVY
HYTTPLTFGG
SAVYYCARVY
HYTTPLTFGG






YSYYSYDATY
GTKLEIK
YSYYSYDATY
GTKLEIKRTV






FDYWGQGTTL

FDYWGQGTTL
AAPSVFIFPP






TVSS

TVSSASTKGP
SDEQLKSGTA








SVFPLAPSSK
SVVCLLNNFY








STSGGTAALG
PREAKVQWKV








CLVKDYFPEP
DNALQSGNSQ








VTVSWNSGAL
ESVTEQDSKD








TSGVHTFPAV
STYSLSSTLT








LQSSGLYSLS
LSKADYEKHK








SVVTVPSSSL
VYACEVTHQG








GTQTYICNVN
LSSPVTKSFN








HKPSNTKVDK
RGEC








KVEPKSCDKT









HTCPPCPAPE









LLGGPSVFLF









PPKPKDTLMI









SRTPEVTCVV









VDVSHEDPEV









KFNWYVDGVE









VHNAKTKPRE









EQYNSTYRVV









SVLTVLHQDW









LNGKEYKCKV









SNKALPAPIE









KTISKAKGQP









REPQVYTLPP









SREEMTKNQV









SLTCLVKGFY









PSDIAVEWES









NGQPENNYKT









TPPVLDSDGS









FFLYSKLTVD









KSRWQQGNVF









SCSVMHEALH









NHYTQKSLSL









SPGK







 983
 984
 985
 986





30
CD8B223
IgG1
Kappa
DVQLQESGPI
DIVMTQSQKF
DVQLQESGPI
DIVMTQSQKF






LVAPSQSLSI
MSTSVGDRVR
LVAPSQSLSI
MSTSVGDRVR






TCTVSGFSLT
VTCKASQNVN
TCTVSGFSLT
VTCKASQNVN






SYSVHWVRQP
TDVAWYQQKP
SYSVHWVRQP
TDVAWYQQKP






PGKGLEWLGV
GQSPKALIYS
PGKGLEWLGV
GQSPKALIYS






IWAGGSTNYN
ASYRYSGVPD
IWAGGSTNYN
ASYRYSGVPD






SAFMSRLTIS
RFTGSGSGTD
SAFMSRLTIS
RFTGSGSGTD






KDNSESQVFL
FTLTISNVQS
KDNSESQVFL
FTLTISNVQS






KMISLQTDDT
EDLAEYFCQQ
KMISLQTDDT
EDLAEYFCQQ






AMYYCAKHSY
CNSYPLTFGA
AMYYCAKHSY
CNSYPLTFGA






YSFDAFDYWG
GTKLELK
YSFDAFDYWG
GTKLELKRTV






QGTTLTVSS

QGTTLTVSSA
AAPSVFIFPP








STKGPSVFPL
SDEQLKSGTA








APSSKSTSGG
SVVCLLNNFY








TAALGCLVKD
PREAKVQWKV








YFPEPVTVSW
DNALQSGNSQ








NSGALTSGVH
ESVTEQDSKD








TFPAVLQSSG
STYSLSSTLT








LYSLSSVVTV
LSKADYEKHK








PSSSLGTQTY
VYACEVTHQG








ICNVNHKPSN
LSSPVTKSFN








TKVDKKVEPK
RGEC








SCDKTHTCPP









CPAPELLGGP









SVFLFPPKPK









DTLMISRTPE









VTCVVVDVSH









EDPEVKFNWY









VDGVEVHNAK









TKPREEQYNS









TYRVVSVLTV









LHQDWLNGKE









YKCKVSNKAL









PAPIEKTISK









AKGQPREPQV









YTLPPSREEM









TKNQVSLTCL









VKGFYPSDIA









VEWESNGQPE









NNYKTTPPVL









DSDGSFFLYS









KLTVDKSRWQ









QGNVFSCSVM









HEALHNHYTQ









KSLSLSPGK







1017
1018
1019
1020





31
CD8B234
IgG1
Kappa
QVQLKESGPG
DIQMTQSSSS
QVQLKESGPG
DIQMTQSSSS






LVKPSQSLSL
FSVSLGDRVT
LVKPSQSLSL
FSVSLGDRVT






TCSVTGYSIT
ITCKASEDIY
TCSVTGYSIT
ITCKASEDIY






SGYYWNWIRQ
NRLAWYQQRP
SGYYWNWIRQ
NRLAWYQQRP






FPGN
GNAPRLLISG
FPGNKLEWMG
GNAPRLLISG






KLEWMGYINY
ATSLETGVPS
YINYDGRNNY
ATSLETGVPS






DGRNNYNPSL
RFSGGGSGKD
NPSLKNRISI
RFSGGGSGKD






KNRISITRDT
YTLSITSLQT
TRDTSKNHFF
YTLSITSLQT






SKNHFFLKLN
EDVANYYCQQ
LKLNSVTTED
EDVANYYCQQ






SVTTEDTATY
YWSFPRTFGG
TATYYCSRDQ
YWSFPRTFGG






YCSRDQGYSK
GTKLEIK
GYSKFYFDYW
GTKLEIKRTV






FYFDYWGQGT

GQGTTLTVSS
AAPSVFIFPP






TLTVSS

ASTKGPSVFP
SDEQLKSGTA








LAPSSKSTSG
SVVCLLNNFY








GTAALGCL
PREAKVQWKV








VKDYFPEPVT
DNALQSGNSQ








VSWNSGALTS
ESVTEQDSKD








GVHTFPAVLQ
STYSLSSTLT








SSGLYSLSSV
LSKADYEKHK








VTVPSSSLGT
VYACEVTHQG








QTYICNVNHK
LSSPVTKSFN








PSNTKVDKKV
RGEC








EPKSCDKTHT









CPPCPAPELL









GGPSVFLFPP









KPKDTLMISR









TPEVTCVVVD









VSHEDPEVKF









NWYVDGVEVH









NAKTKPREEQ









YNSTYRVVSV









LTVLHQDWLN









GKEYKCKVSN









KALPAPIEKT









ISKAKGQPRE









PQVYTLPPSR









EEMTKNQVSL









TCLVKGFYPS









DIAVEWESNG









QPENNYKTTP









PVLDSDGSFF









LYSKLTVDKS









RWQQGNVFSC









SVMHEALHNH









YTQKSLSLSP









GK







1051
1052
1053
1054





32
CD8B251
IgG1
Kappa
QVQLKGSGPG
DIKMTQSQKF
QVQLKGSGPG
DIKMTQSQKF






LVQPSQSLSI
MSTTVGDRVS
LVQPSQSLSI
MSTTVGDRVS






TCTVSGFSLT
ITCKASQNVG
TCTVSGFSLT
ITCKASQNVG






TYAVHWVRQS
TAVAWYQQKP
TYAVHWVRQS
TAVAWYQQKP






PGKGLEWLGV
GQSPKLLIYS
PGKGLEWLGV
GQSPKLLIYS






IWSGGSTDYN
ASNRYTGVPD
IWSGGSTDYN
ASNRYTGVPD






AAFISRLSIS
RFTGSGSGTD
AAFISRLSIS
RFTGSGSGTD






KDNSKSQVFF
FTLTISNMQS
KDNSKSQVFF
FTLTISNMQS






KMNSLQADDT
EDLADYFCQQ
KMNSLQADDT
EDLADYFCQQ






AIYYCARHSY
YSSYPFTFGS
AIYYCARHSY
YSSYPFTFGS






YHYNAMDNWG
GTKLEIK
YHYNAMDNWG
GTKLEIKRTV






QGTSVTVSS

QGTSVTVSSA
AAPSVFIFPP








STKGPSVFPL
SDEQLKSGTA








APSSKSTSGG
SVVCLLNNFY








TAALGCLVKD
PREAKVQWKV








YFPEPVTVSW
DNALQSGNSQ








NSGALTSGVH
ESVTEQDSKD








TFPAVLQSSG
STYSLSSTLT








LYSLSSVVTV
LSKADYEKHK








PSSSLGTQTY
VYACEVTHQG








ICNVNHKPSN
LSSPVTKSFN








TKVDKKVEPK
RGEC








SCDKTHTCPP









CPAPELLGGP









SVFLFPPKPK









DTLMISRTPE









VTCVVVDVSH









EDPEVKFNWY









VDGVEVHNAK









TKPREEQYNS









TYRVVSVLTV









LHQDWLNGKE









YKCKVSNKAL









PAPIEKTISK









AKGQPREPQV









YTLPPSREEM









TKNQVSLTCL









VKGFYPSDIA









VEWESNGQPE









NNYKTTPPVL









DSDGSFFLYS









KLTVDKSRWQ









QGNVFSCSVM









HEALHNHYTQ









KSLSLSPGK







1085
1086
1087
1088





33
CD8B269
IgG1
Kappa
DVQLQESGPG
DIVMTQSQKF
DVQLQESGPG
DIVMTQSQKF






LVKPSQSLSL
MSTSVGDRVR
LVKPSQSLSL
MSTSVGDRVR






TCSVTGYSIT
VTCKASQNVG
TCSVTGYSIT
VTCKASQNVG






SGYYWNWIRQ
TDVAWYQQKP
SGYYWNWIRQ
TDVAWYQQKP






FPGNKLEWMG
GQSPKALIYS
FPGNKLEWMG
GQSPKALIYS






YISYDGSNNY
ASYRYSGVPD
YISYDGSNNY
ASYRYSGVPD






NPSLKNRISI
RFTGSGSGTD
NPSLKNRISI
RFTGSGSGTD






TRDTSKNQFF
FTLTISDVQS
TRDTSKNQFF
FTLTISDVQS






LKLNSVTTED
EDLAEYFCQQ
LKLNSVTTED
EDLAEYFCQQ






TATYYCVRNH
YKSYPLTFGA
TATYYCVRNH
YKSYPLTFGA






GDAMDHWGQG
GTKLELK
GDAMDHWGQG
GTKLELKRTV






TTLTVSS

TTLTVSSAST
AAPSVFIFPP








KGPSVFPLAP
SDEQLKSGTA








SSKSTSGGTA
SVVCLLNNFY








ALGCLVKDYF
PREAKVQWKV








PEPVTVSWNS
DNALQSGNSQ








GALTSGVHTF
ESVTEQDSKD








PAVLQSSGLY
STYSLSSTLT








SLSSVVTVPS
LSKADYEKHK








SSLGTQTYIC
VYACEVTHQG








NVNHKPSNTK
LSSPVTKSFN








VDKKVEPKSC
RGEC








DKTHTCPPCP









APELLGGPSV









FLFPPKPKDT









LMISRTPEVT









CVVVDVSHED









PEVKFNWYVD









GVEVHNAKTK









PREEQYNSTY









RVVSVLTVLH









QDWLNGKEYK









CKVSNKALPA









PIEKTISKAK









GQPREPQVYT









LPPSREEMTK









NQVSLTCLVK









GFYPSDIAVE









WESNGQPENN









YKTTPPVLDS









DGSFFLYSKL









TVDKSRWQQG









NVFSCSVMHE









ALHNHYTQKS









LSLSPGK







1119
1120
1121
1122





34
CD8B290
IgG1
Kappa
QVQLKESGPG
DIVMTQSHKF
QVQLKESGPG
DIVMTQSHKF






LVAPSQSLSI
MSTSVGDRVS
LVAPSQSLSI
MSTSVGDRVS






TCTVSGFSLS
ITCKASQDVG
TCTVSGFSLS
ITCKASQDVG






RYSVHWVRQP
TVVAWYQQKP
RYSVHWVRQP
TVVAWYQQKP






PGKGLVWLGM
GQSPKLLIFW
PGKGLVWLGM
GQSPKLLIFW






IWGGGSTDYN
TSTRHTGVPD
IWGGGSTDYN
TSTRHTGVPD






SALKSRLSIS
RFTGSGSGTD
SALKSRLSIS
RFTGSGSGTD






KDNSKSQVFL
FTLTISNVQS
KDNSKSQVFL
FTLTISNVQS






KMNSLQTDDT
EDLADYFCQQ
KMNSLQTDDT
EDLADYFCQQ






AMYYCARIYF
YSSYPYTFGS
AMYYCARIYF
YSSYPYTFGS






DNYVGFAYWG
GTKLELK
DNYVGFAYWG
GTKLELKRTV






QGTTLTVSS

QGTTLTVSSA
AAPSVFIFPP








STKGPSVFPL
SDEQLKSGTA








APSSKSTSGG
SVVCLLNNFY








TAALGCLVKD
PREAKVQWKV








YFPEPVTVSW
DNALQSGNSQ








NSGALTSGVH
ESVTEQDSKD








TFPAVLQSSG
STYSLSSTLT








LYSLSSVVTV
LSKADYEKHK








PSSSLGTQTY
VYACEVTHQG








ICNVNHKPSN
LSSPVTKSFN








TKVDKKVEPK
RGEC








SCDKTHTCPP









CPAPELLGGP









SVFLFPPKPK









DTLMISRTPE









VTCVVVDVSH









EDPEVKFNWY









VDGVEVHNAK









TKPREEQYNS









TYRVVSVLTV









LHQDWLNGKE









YKCKVSNKAL









PAPIEKTISK









AKGQPREPQV









YTLPPSREEM









TKNQVSLTCL









VKGFYPSDIA









VEWESNGQPE









NNYKTTPPVL









DSDGSFFLYS









KLTVDKSRWQ









QGNVFSCSVM









HEALHNHYTQ









KSLSLSPGK







1153
1154
1155
1156





35
CD8B310
IgG1
Kappa
QVQLKESGPG
DVLMTQTPLS
QVQLKESGPG
DVLMTQTPLS






LVAPSQSLSI
LPVSLGDQAS
LVAPSQSLSI
LPVSLGDQAS






TCTVSGFSLT
ISCRSSQTIV
TCTVSGFSLT
ISCRSSQTIV






NYAVHWVRQS
HSNGNTYLEW
NYAVHWVRQS
HSNGNTYLEW






PGKGLEWLGV
YLQKPGQSPK
PGKGLEWLGV
YLQKPGQSPK






IWTDGSTDYN
LLMYKVSNRF
IWTDGSTDYN
LLMYKVSNRF






AGFISRLSIS
SGVPDRFGGS
AGFISRLSIS
SGVPDRFGGS






KDNSKSQVFF
GSGTDFTLKI
KDNSKSQVFF
GSGTDFTLKI






KMNSLQADDT
SRVEAEDLGV
KMNSLQADDT
SRVEAEDLGV






AIYYCARNNG
YYCFQGSHAP
AIYYCARNNG
YYCFQGSHAP






YFPAFFAYWG
FTFGSGTKLE
YFPAFFAYWG
FTFGSGTKLE






QGTTVTVSS
IK
QGTTVTVSSA
IKRTVAAPSV








STKGPSVFPL
FIFPPSDEQL








APSSKSTSGG
KSGTASVVCL








TAALGCLVKD
LNNFYPREAK








YFPEPVTVSW
VQWKVDNALQ








NSGALTSGVH
SGNSQESVTE








TFPAVLQSSG
QDSKDSTYSL








LYSLSSVVTV
SSTLTLSKAD








PSSSLGTQTY
YEKHKVYACE








ICNVNHKPSN
VTHQGLSSPV








TKVDKKVEPK
TKSFNRGEC








SCDKTHTCPP









CPAPELLGGP









SVFLFPPKPK









DTLMISRTPE









VTCVVVDVSH









EDPEVKFNWY









VDGVEVHNAK









TKPREEQYNS









TYRVVSVLTV









LHQDWLNGKE









YKCKVSNKAL









PAPIEKTISK









AKGQPREPQV









YTLPPSREEM









TKNQVSLTCL









VKGFYPSDIA









VEWESNGQPE









NNYKTTPPVL









DSDGSFFLYS









KLTVDKSRWQ









QGNVFSCSVM









HEALHNHYTQ









KSLSLSPGK







1187
1188
1189
1190





36
CD8B352
IgG1
Kappa
QVQLKESGPG
DIQMTQSSSS
QVQLKESGPG
DIQMTQSSSS






LVKPSQSLSL
FSVSLGDRVT
LVKPSQSLSL
FSVSLGDRVT






TCSVTGYSIT
ITCKASEDIY
TCSVTGYSIT
ITCKASEDIY






SGYYWNWIRQ
NRLAWYQQRP
SGYYWNWIRQ
NRLAWYQQRP






FPGNKLEWMG
GNAPRLLISG
FPGNKLEWMG
GNAPRLLISG






YINYDGRNNY
ATSLETGVPS
YINYDGRNNY
ATSLETGVPS






NPSLRNRISI
RFSGSGSGKD
NPSLRNRISI
RFSGSGSGKD






TRDTSKNHFF
YTLSITSLQT
TRDTSKNHFF
YTLSITSLQT






LKLNSVTTED
EDVANYYCQQ
LKLNSVTTED
EDVANYYCQQ






TATYYCARDQ
YWSFPRTFGG
TATYYCARDQ
YWSFPRTFGG






GYSKFYFDYW
GTKLEIK
GYSKFYFDYW
GTKLEIKRTV






GQGTTLTVSS

GQGTTLTVSS
AAPSVFIFPP








ASTKGPSVFP
SDEQLKSGTA








LAPSSKSTSG
SVVCLLNNFY








GTAALGCLVK
PREAKVQWKV








DYFPEPVTVS
DNALQSGNSQ








WNSGALTSGV
ESVTEQDSKD








HTFPAVLQSS
STYSLSSTLT








GLYSLSSVVT
LSKADYEKHK








VPSSSLGTQT
VYACEVTHQG








YICNVNHKPS
LSSPVTKSFN








NTKVDKKVEP
RGEC








KSCDKTHTCP









PCPAPELLGG









PSVFLFPPKP









KDTLMISRTP









EVTCVVVDVS









HEDPEVKFNW









YVDGVEVHNA









KTKPREEQYN









STYRVVSVLT









VLHQDWLNGK









EYKCKVSNKA









LPAPIEKTIS









KAKGQPREPQ









VYTLPPSREE









MTKNQVSLTC









LVKGFYPSDI









AVEWESNGQP









ENNYKTTPPV









LDSDGSFFLY









SKLTVDKSRW









QQGNVFSCSV









MHEALHNHYT









QKSLSLSPGK







1221
1222
1223
1224





37
CD8B319
IgG1
Kappa
QVQLKESGPE
DIVMTQSQKF
QVQLKESGPE
DIVMTQSQKF






LKKPGETVKI
MSTTVGDRVS
LKKPGETVKI
MSTTVGDRVS






SCKASGYSFT
ITCKASQNVG
SCKASGYSFT
ITCKASQNVG






AYYMHWVKQS
TAVAWYQQKP
AYYMHWVKQS
TAVAWYQQKP






PEKSLEWIGE
GQSPKLLIYS
PEKSLEWIGE
GQSPKLLIYS






INPSAGGTTY
ASYRYTGVPD
INPSAGGTTY
ASYRYTGVPD






NQKFKAKATL
RFTGSGSGTH
NQKFKAKATL
RFTGSGSGTH






TVDKSSSTAF
FTLTISNIQS
TVDKSSSTAF
FTLTISNIQS






IQLKSLTSED
EDLADYFCQQ
IQLKSLTSED
EDLADYFCQQ






SAVYYCARWT
YNNYLTFGSG
SAVYYCARWT
YNNYLTFGSG






NPFDYWGQGT
TKLEIK
NPFDYWGQGT
TKLEIKRTVA






TLTVSS

TLTVSSASTK
APSVFIFPPS








GPSVFPLAPS
DEQLKSGTAS








SKSTSGGTAA
VVCLLNNFYP








LGCLVKDYFP
REAKVQWKVD








EPVTVSWNSG
NALQSGNSQE








ALTSGVHTFP
SVTEQDSKDS








AVLQSSGLYS
TYSLSSTLTL








LSSVVTVPSS
SKADYEKHKV








SLGTQTYICN
YACEVTHQGL








VNHKPSNTKV
SSPVTKSFNR








DKKVEPKSCD
GEC








KTHTCPPCPA









PELLGGPSVF









LFPPKPKDTL









MISRTPEVTC









VVVDVSHEDP









EVKFNWYVDG









VEVHNAKTKP









REEQYNSTYR









VVSVLTVLHQ









DWLNGKEYKC









KVSNKALPAP









IEKTISKAKG









QPREPQVYTL









PPSREEMTKN









QVSLTCLVKG









FYPSDIAVEW









ESNGQPENNY









KTTPPVLDSD









GSFFLYSKLT









VDKSRWQQGN









VFSCSVMHEA









LHNHYTQKSL









SLSPGK







1255
1256
1257
1258





38
CD8B194
IgG1
Kappa
QVQLQQPGAE
DIVMTQSQKF
QVQLQQPGAE
DIVMTQSQKF






LVKPGASVKL
MSTTVGDRVS
LVKPGASVKL
MSTTVGDRVS






SCKASGYTFT
ITCKASQNVG
SCKASGYTFT
ITCKASQNVG






SYWINWVKQR
TAVAWYQQKP
SYWINWVKQR
TAVAWYQQKP






PGQGLEWIGN
GQSPKLLIYS
PGQGLEWIGN
GQSPKLLIYS






IYPGSSSTNY
ASNRYTGVPD
IYPGSSSTNY
ASNRYTGVPD






NEKFKSKATL
RFTGSGSGTD
NEKFKSKATL
RFTGSGSGTD






TVDTSSSAAY
FTLTISNMQS
TVDTSSSAAY
FTLTISNMQS






MQLSSLTSGD
EDLADYFCQQ
MQLSSLTSGD
EDLADYFCQQ






SAVYYCAREL
YSSYPFTFGS
SAVYYCAREL
YSSYPFTFGS






GPYYRYSAMV
GTKLEIK
GPYYRYSAMV
GTKLEIKRTV






YWGQGTTVTV

YWGQGTTVTV
AAPSVFIFPP






SS

SSASTKGPSV
SDEQLKSGTA








FPLAPSSKST
SVVCLLNNFY








SGGTAALGCL
PREAKVQWKV








VKDYFPEPVT
DNALQSGNSQ








VSWNSGALTS
ESVTEQDSKD








GVHTFPAVLQ
STYSLSSTLT








SSGLYSLSSV
LSKADYEKHK








VTVPSSSLGT
VYACEVTHQG








QTYICNVNHK
LSSPVTKSFN








PSNTKVDKKV
RGEC








EPKSCDKTHT









CPPCPAPELL









GGPSVFLFPP









KPKDTLMISR









TPEVTCVVVD









VSHEDPEVKF









NWYVDGVEVH









NAKTKPREEQ









YNSTYRVVSV









LTVLHQDWLN









GKEYKCKVSN









KALPAPIEKT









ISKAKGQPRE









PQVYTLPPSR









EEMTKNQVSL









TCLVKGFYPS









DIAVEWESNG









QPENNYKTTP









PVLDSDGSFF









LYSKLTVDKS









RWQQGNVFSC









SVMHEALHNH









YTQKSLSLSP









GK







1289
1290
1291
1292





39
CD8B231
IgG1
Kappa
EVKLVESGAE
DIQMTQTTSS
EVKLVESGAE
DIQMTQTTSS






LVKPGASVKL
LSASLGDRVT
LVKPGASVKL
LSASLGDRVT






SCKASGYTFT
ITCRASQDIN
SCKASGYTFT
ITCRASQDIN






NYWMHWVKQR
IYLNWYQQKP
NYWMHWVKQR
IYLNWYQQKP






PGQGLEVJIG
EGSIKCLIYH
PGQGLEWIGN
EGSIKCLIYH






NIDPSDSETH
TSRLHSGVPS
IDPSDSETHY
TSRLHSGVPS






YNQKFKDKAT
RFSGSGSGTD
NQKFKDKATL
RFSGSGSGTD






LTVDKSSSTA
YSLTISNLEQ
TVDKSSSTAY
YSLTISNLEQ






YMQLSSLTS
EDIATYFCQQ
MQLSSLTSED
EDIATYFCQQ






EDSAVYYCAS
DNTLPYTFGS
SAVYYCASGL
DNTLPYTFGS






GLTGTGHYWG
GTKLEIK
TGTGHYWGQG
GTKLEIKRTV






QGTTLTVSS

TTLTVSSAST
AAPSVFIFPP








KGPSVFPLAP
SDEQLKSGTA








SSKSTSGGTA
SVVCLLNNFY








ALGCLVKDYF
PREAKVQWKV








PEPVTVSWNS
DNALQSGNSQ








GALTSGVHTF
ESVTEQDSKD








PAVLQSSGLY
STYSLSSTLT








SLSSVVTVPS
LSKADYEKHK








SSLGTQTYIC
VYACEVTHQG








NVNHKPSNTK
LSSPVTKSFN








VDKKVEPKSC
RGEC








DKTHTCPPCP









APELLGGPSV









FLFPPKPKDT









LMISRTPEVT









CVVVDVSHED









PEVKFNWYVD









GVEVHNAKTK









PREEQY









NSTYRVVSVL









TVLHQDWLNG









KEYKCKVSNK









ALPAPIEKTI









SKAKGQPREP









QVYTLPPSRE









EMTKNQVSLT









CLVKGFYPSD









IAVEWESNGQ









PENNYKTTPP









VLDSDGSFFL









YSKLTVDKSR









WQQGNVFSCS









VMHEALHNHY









TQKSLSLSPG









K







1323
1324
1325
1326





40
CD8B238
IgG1
Kappa
EFQLQQSGPE
DIKMTQSPSS
EFQLQQSGPE
DIKMTQSPSS






LVKPGASLKI
MCPSLGERVT
LVKPGASLKI
MCPSLGERVT






SCKASGYTFT
ITCKASQDIK
SCKASGYTFT
ITCKASQDIK






DYSMDWVKQS
SYLSWFQQKP
DYSMDWVKQS
SYLSWFQQKP






HGKTLEWIGY
GKSPKTLIYR
HGKTLEWIGY
GKSPKTLIYR






IYTYSGGAGY
ANRLVDGVPS
IYTYSGGAGY
ANRLVDGVPS






NRKFKSKATL
RFSGSGSGQD
NRKFKSKATL
RFSGSGSGQD






TVDKSSSTAY
YSLTISSLEY
TVDKSSSTAY
YSLTISSLEY






LELHSLTSDD
EDMGIYYCLQ
LELHSLTSDD
EDMGIYYCLQ






SAVYYCARDS
YDEFRTFGGG
SAVYYCARDS
YDEFRTFGGG






SDYEFAYWGQ
TKLEIK
SDYEFAYWGQ
TKLEIKRTVA






GTLVTVSA

GTLVTVSAAS
APSVFIFPPS








TKGPSVFPLA
DEQLKSGTAS








PSSKSTSGGT
VVCLLNNFYP








AALGCLVKDY
REAKVQWKVD








FPEPVTVSWN
NALQSGNSQE








SGALTSGVHT
SVTEQDSKDS








FPAVLQSSGL
TYSLSSTLTL








YSLSSVVTVP
SKADYEKHKV








SSSLGTQTYI
YACEVTHQGL








CNVNHKPSNT
SSPVTKSFNR








KVDKKVEPKS
GEC








CDKTHTCPPC









PAPELLGGPS









VFLFPPKPKD









TLMISRTPEV









TCVVVDVSHE









DPEVKFNWYV









DGVEVHNAKT









KPREEQYNST









YRVVSVLTVL









HQDWLNGKEY









KCKVSNKALP









APIEKTISKA









KGQPREPQVY









TLPPSREEMT









KNQVSLTCLV









KGFYPSDIAV









EWESNGQPEN









NYKTTPPVLD









SDGSFFLYSK









LTVDKSRWQQ









GNVFSCSVMH









EALHNHYTQK









SLSLSPGK







1357
1358
1359
1360





41
CD8B255
IgG1
Kappa
QVTLKESGPG
DIQMTQSPAS
QVTLKESGPG
DIQMTQSPAS






ILQPSQTLSL
LSVSVGETVT
ILQPSQTLSL
LSVSVGETVT






TCSFSGFSLN
ITCRASENIY
TCSFSGFSLN
ITCRASENIY






TSGMGVSWIR
SDLAWYQQKQ
TSGMGVSWIR
SDLAWYQQKQ






KPSGKGLEWL
GKSPQLLVYA
KPSGKGLEWL
GKSPQLLVYA






AHIFWDDDKR
ATILTDGVPS
AHIFWDDDKR
ATILTDGVPS






YNPSLKSRLT
RFSGSGSGTQ
YNPSLKSRLT
RFSGSGSGTQ






ISKDTSSNQV
YSLKINSLQS
ISKDTSSNQV
YSLKINSLQS






FLMITSVDTA
EDFGNYYCQH
FLMITSVDTA
EDFGNYYCQH






DTATYYCARR
FWGTPWTFGD
DTATYYCARR
FWGTPWTFGD






DGYGDYAYFD
GTRLEIK
DGYGDYAYFD
GTRLEIKRTV






VWGAGTLVTV

VWGAGTLVTV
AAPSVFIFPP






SA

SAASTKGPSV
SDEQLKSGTA








FPLAPSSKST
SVVCLLNNFY








SGGTAALGCL
PREAKVQWKV








VKDYFPEPVT
DNALQSGNSQ








VSWNSGALTS
ESVTEQDSKD








GVHTFPAVLQ
STYSLSSTLT








SSGLYSLSSV
LSKADYEKHK








VTVPSSSLGT
VYACEVTHQG








QTYICNVNHK
LSSPVTKSFN








PSNTKVDKKV
RGEC








EPKSCDKTHT









CPPCPAPELL









GGPSVFLFPP









KPKDTLMISR









TPEVTCVVVD









VSHEDPEVKF









NWYVDGVEVH









NAKTKPREEQ









YNSTYRVVSV









LTVLHQDWLN









GKEYKCKVSN









KALPAPIEKT









ISKAKGQPRE









PQVYTLPPSR









EEMTKNQVSL









TCLVKGFYPS









DIAVEWESNG









QPENNYKTTP









PVLDSDGSFF









LYSKLTVDKS









RWQQGNVFSC









SVMHEALHNH









YTQKSLSLSP









GK







1391
1392
1393
1394





42
CD8B324
IgG1
Kappa
QVQLQQPGAD
DIVMTQSQKF
QVQLQQPGAD
DIVMTQSQKF






LVKPGASVKL
MPTTVGDRVS
LVKPGASVKL
MPTTVGDRVS






SCKASGYTST
ITCKASQNVG
SCKASGYTST
ITCKASQNVG






SHWIHWVKQR
TAVAWYQQKP
SHWIHWVKQR
TAVAWYQQKP






PGQGLEWIGN
GQSPKLLIAS
PGQGLEWIGN
GQSPKLLIAS






IYPGS
ASNRYTGVPD
IYPGSSSTNY
ASNRYTGVPD






SSTNYNEKFK
RFTGSGSGTD
NEKFKRMATL
RFTGSGSGTD






RMATLTVDTS
FTLTISTMQS
TVDTSSSTVY
FTLTISTMQS






SSTVYMVLSS
EDLADYFCQQ
MVLSSLTSDD
EDLADYFCQQ






LTSDDSAVYY
YSTYPLTFGA
SAVYYCARHS
YSTYPLTFGA






CARHSPGHRD
GTKLEMK
PGHRDYAMDY
GTKLEMKRTV






YAMDYWGLGT

WGLGTSVTVS
AAPSVFIFPP






SVTVSS

SASTKGPSVF
SDEQLKSGTA








PLAPSSKSTS
SVVCLLNNFY








GGTAALGCLV
PREAKVQWKV








KDYFPEPVTV
DNALQSGNSQ








SWNSGALTSG
ESVTEQDSKD








VHTFPAVLQS
STYSLSSTLT








SGLYS
LSKADYEKHK








LSSVVTVPSS
VYACEVTHQG








SLGTQTYICN
LSSPVTKSFN








VNHKPSNTKV
RGEC








DKKVEPKSCD









KTHTCPPCPA









PELLGGPSVF









LFPPKPKDTL









MISRTPEVTC









VVVDVSHEDP









EVKFNWYVDG









VEVHNAKTKP









REEQYNSTYR









VVSVLTVLHQ









DWLNGKEYKC









KVSNKALPAP









IEKTISKAKG









QPREPQVYTL









PPSREEMTKN









QVSLTCLVKG









FYPSDIAVEW









ESNGQPENNY









KTTPPVLDSD









GSFFLYSKLT









VDKSRWQQGN









VFSCSVMHEA









LHNHYTQKSL









SLSPGK







1425
1426
1427
1428





43
CD8B337
IgG1
Kappa
QVTLKESGPG
DIQMTQYPAS
QVTLKESGPG
DIQMTQYPAS






KVQPSQTLSL
LSVSVGETVT
KVQPSQTLSL
LSVSVGETVT






TCSFSGFSLS
ITCRASENIY
TCSFSGFSLS
ITCRASENIY






TSGMGVSWIR
SDLAWYQQKQ
TSGMGVSWIR
SDLAWYQQKQ






KPSGKGLEWL
GKSPQLLVYA
KPSGKGLEWL
GKSPQLLVYA






AHIFWDDDRR
ATNLADGVPS
AHIFWDDDRR
ATNLADGVPS






YKSSLKSRLT
RFSGSGSGTQ
YKSSLKSRLT
RFSGSGSGTQ






ISKDTSSNQV
YSLKINSLQS
ISKDTSSNQV
YSLKINSLQS






FLMITSVDTA
EDFGNYYCQH
FLMITSVDTA
EDFGNYYCQH






DSATYYCARR
FWGTPWTFGG
DSATYYCARR
FWGTPWTFGG






VGYGDYAYFD
GTKLEIK
VGYGDYAYFD
GTKLEIKRTV






VWGAGTTVTV

VWGAGTTVTV
AAPSVFIFPP






SS

SSASTKGPSV
SDEQLKSGTA








FPLAPSSKST
SVVCLLNNFY








SGGTAALGCL
PREAKVQWKV








VKDYFPEPVT
DNALQSGNSQ








VSWNSGALTS
ESVTEQDSKD








GVHTFPAVLQ
STYSLSSTLT








SSGLYSLSSV
LSKADYEKHK








VTVPSSSLGT
VYACEVTHQG








QTYICNVNHK
LSSPVTKSFN








PSNTKVDKKV
RGEC








EPKSCDKTHT









CPPCPAPELL









GGPSVFLFPP









KPKDTLMISR









TPEVTCVVVD









VSHEDPEVKF









NWYVDGVEVH









NAKTKPREEQ









YNSTYRVVSV









LTVLHQDWLN









GKEYKCKVSN









KALPAPIEKT









ISKAKGQPRE









PQVYTLPPSR









EEMTKNQVSL









TCLVKGFYPS









DIAVEWESNG









QPENNYKTTP









PVLDSDGSFF









LYSKLTVDKS









RWQQGNVFSC









SVMHEALHNH









YTQKSLSLSP









GK







1459
1460
1461
1462





44
CD8B344
IgG1
Kappa
QVQLQQSGAE
DIKMTQSQKF
QVQLQQSGAE
DIKMTQSQKF






LVKPGASVKL
MSTTVGDRVS
LVKPGASVKL
MSTTVGDRVS






SCKASGYSFT
ITCKASQNVG
SCKASGYSFT
ITCKASQNVG






NYWINWMKQR
TAVAWYQQKP
NYWINWMKQR
TAVAWYQQKP






PGQGLEWIGN
GQSPKLLIYS
PGQGLEWIGN
GQSPKLLIYS






IYPGSDSSNY
ASNRYTGVPD
IYPGSDSSNY
ASNRYTGVPD






NEKFKTKATL
RFTGSGSGTD
NEKFKTKATL
RFTGSGSGTD






TVDTSSSTAY
FTLTFSNMQS
TVDTSSSTAY
FTLTFSNMQS






MQLSSLTSDD
EDLADYFCQQ
MQLSSLTSDD
EDLADYFCQQ






SAVYYCAREE
YSSYPLTFGA
SAVYYCAREE
YSSYPLTFGA






ADYRYTWFVY
GTKLEMK
ADYRYTWFVY
GTKLEMKRTV






WGQGTLVTVS

WGQGTLVTVS
AAPSVFIFPP






A

AASTKGPSVF
SDEQLKSGTA








PLAPSSKSTS
SVVCLLNNFY








GGTAALGCLV
PREAKVQWKV








KDYFPEPVTV
DNALQSGNSQ








SWNSGALTSG
ESVTEQDSKD








VHTFPAVLQS
STYSLSSTLT








SGLYSLSSVV
LSKADYEKHK








TVPSSSLGTQ
VYACEVTHQG








TYICNVNHKP
LSSPVTKSFN








SNTKVDKKVE
RGEC








PKSCDKTHTC









PPCPAPELLG









GPSVFLFPPK









PKDTLMISRT









PEVTCVVVDV









SHEDPEVKFN









WYVDGVEVHN









AKTKPREEQY









NSTYRVVSVL









TVLHQDWLNG









KEYKCKVSNK









ALPAPIEKTI









SKAKGQPREP









QVYTLPPSRE









EMTKNQVSLT









CLVKGFYPSD









IAVEWESNGQ









PENNYKTTPP









VLDSDGSFFL









YSKLTVDKSR









WQQGNVFSCS









VMHEALHNHY









TQKSLSLSPG









K







1493
1494
1495
1496





45
CD8B264
IgG1
Kappa
EVQLQQSGTE
DIVMTQSQKF
EVQLQQSGTE
DIVMTQSQKF






LVKPGASVKL
MSTTVGDRVS
LVKPGASVKL
MSTTVGDRVS






SC
ITCKASQNVG
SCKASGYSFT
ITCKASQNVG






KASGYSFTSY
TAVAWYQQKP
SYWINWVKQR
TAVAWYQQKP






WINWVKQRPG
GQSPKLLIYS
PGQGPEWIGN
GQSPKLLIYS






QGPEWIGNIY
ASNRYNGVPD
IYPGSSSTNY
ASNRYNGVPD






PGSSSTNYNE
RFTGSGSGTD
NEKFKNKATL
RFTGSGSGTD






KFKNKATLTV
FTLTISNMQS
TVDT
FTLTISNMQS






DTSSSTAYMQ
EDLADYFCQQ
SSSTAYMQLS
EDLADYFCQQ






LSSLTSDDSA
YSTYPYTFGS
SLTSDDSAVY
YSTYPYTFGS






VYYCAREEYS
GTKLEIK
YCAREEYSYK
GTKLEIKRTV






YKSSWFAYWG

SSWFAYWGQG
AAPSVFIFPP






QGTLVTVSA

TLVTVSAAST
SDEQLKSGTA








KGPSVFPLAP
SVVCLLNNFY








SSKSTSGGTA
PREAKVQWKV








ALGCLVKDYF
DNALQSGNSQ








PEPVTVSWNS
ESVTEQDSKD








GALTSGVHTF
STYSLSSTLT








PAVLQSSGLY
LSKADYEKHK








SLSSVVTVPS
VYACEVTHQG








SSLGTQTYIC
LSSPVTKSFN








NVNHKPSNTK
RGEC








VDKKVEPKSC









DKTHTCPPCP









APELLGGPSV









FLFPPKPKDT









LMISRTPEVT









CVVVDVSHED









PEVKFNWYVD









GVEVHNAKTK









PREEQYNSTY









RVVSVLTVLH









QDWLNGKEYK









CKVSNKALPA









PIEKTISKAK









GQPREPQVYT









LPPSREEMTK









NQVSLTCLVK









GFYPSDIAVE









WESNGQPENN









YKTTPPVLDS









DGSFFLYSKL









TVDKSRWQQG









NVFSCSVMHE









ALHNHYTQKS









LSLSPGK







1527
1528
1529
1530





46
CD8B318
IgG1
Kappa
EVQLQQSGAE
DIVMTQSQKF
EVQLQQSGAE
DIVMTQSQKF






LVKPGASVKL
MSTTIGDRVS
LVKPGASVKL
MSTTIGDRVS






SCKASGYTFT
ITCKASQNVG
SCKASGYTFT
ITCKASQNVG






SYWISWVKQR
TAVAWFQQKP
SYWISWVKQR
TAVAWFQQKP






PGQGLEWIGN
GQSPKLLIYS
PGQGLEWIGN
GQSPKLLIYS






IYPGSSSSNY
ASNRYTGVPD
IYPGSSSSNY
ASNRYTGVPD






NENFKSKATL
RFTGSGSGTD
NENFKSKATL
RFTGSGSGTD






TVDTSSSTAH
FTLTISNMQS
TVDTSSSTAH
FTLTISNMQS






MQLSSLTSDD
EDLANYFCQQ
MQLSSLTSDD
EDLANYFCQQ






SAVFYCAREE
YSTYPFTFGG
SAVFYCAREE
YSTYPFTFGG






YSYFPSWFAY
GTKLEIK
YSYFPSWFAY
GTKLEIKRTV






WGQGTSVTVS

WGQGTSVTVS
AAPSVFIFPP






S

SASTKGPSVF
SDEQLKSGTA








PLAPSSKSTS
SVVCLLNNFY








GGTAALGCLV
PREAKVQWKV








KDYFPEPVTV
DNALQSGNSQ








SWNSGALTSG
ESVTEQDSKD








VHTFPAVLQS
STYSLSSTLT








SGLYSLSSVV
LSKADYEKHK








TVPSSSLGTQ
VYACEVTHQG








TYICNVNHKP
LSSPVTKSFN








SNTKVDKKVE
RGEC








PKSCDKTHTC









PPCPAPELLG









GPSVFLFPPK









PKDTLMISRT









PEVTCVVVDV









SHEDPEVKFN









WYVDGVEVHN









AKTKPREEQY









NSTYRVVSVL









TVLHQDWLNG









KEYKCKVSNK









ALPAPIEKTI









SKAKGQPREP









QVYTLPPSRE









EMTKNQVSLT









CLVKGFYPSD









IAVEWESNGQ









PENNYKTTPP









VLDSDGSFFL









YSKLTVDKSR









WQQGNVFSCS









VMHEALHNHY









TQKSLSLSPG









K







1561
1562
1563
1564





47
CD8B333
IgG1
Kappa
QVQLQQPGTE
DIVMTQSQKF
QVQLQQPGTE
DIVMTQSQKF






LVKPGASVKL
MSTTVGDRVS
LVKPGASVKL
MSTTVGDRVS






SCKASGYSFA
ITCKASQNVG
SCKASGYSFA
ITCKASQNVG






SFWINWVKQR
TAVAWYQQKP
SFWINWVKQR
TAVAWYQQKP






PGQGPEWIGN
GQSPKLLIYS
PGQGPEWIGN
GQSPKLLIYS






IYPGSSSTNY
ASNRYNGVPD
IYPGSSSTNY
ASNRYNGVPD






SEKFKNKATL
RFTGSGSGTD
SEKFKNKATL
RFTGSGSGTD






TVDKSSSTAY
FTLTISNMQS
TVDKSSSTAY
FTLTISNMQS






MQLSSLTSDD
EDLADYFCQQ
MQLSSLTSDD
EDLADYFCQQ






SAVYYCAREE
YSTYPYTFGS
SAVYYCAREE
YSTYPYTFGS






YSYKSSWFAY
GTKLELK
YSYKSSWFAY
GTKLELKRTV






WGQGTTVTVS

WGQGTTVTVS
AAPSVFIFPP






S

SASTKGPSVF
SDEQLKSGTA








PLAPSSKSTS
SVVCLLNNFY








GGTAALGCLV
PREAKVQWKV








KDYFPEPVTV
DNALQSGNSQ








SWNSGALTSG
ESVTEQDSKD








VHTFPAVLQS
STYSLSSTLT








SGLYSLSSVV
LSKADYEKHK








TVPSSSLGTQ
VYACEVTHQG








TYICNVNHKP
LSSPVTKSFN








SNTKVDKKVE
RGEC








PKSCDKTHTC









PPCPAPELLG









GPSVFLFPPK









PKDTLMISRT









PEVTCVVVDV









SHEDPEVKFN









WYVDGVEVHN









AKTKPREEQY









NSTYRVVSVL









TVLHQDWLNG









KEYKCKVSNK









ALPAPIEKTI









SKAKGQPREP









QVYTLPPSRE









EMTKNQVSLT









CLVKGFYPSD









IAVEWESNGQ









PENNYKTTPP









VLDSDGSFFL









YSKLTVDKSR









WQQGNVFSCS









VMHEALHNHY









TQKSLSLSPG









K







1595
1596
1597
1598





48
CD8B366
IgG1
Kappa
EVQLQQSGPE
DIKMTQSPSY
EVQLQQSGPE
DIKMTQSPSY






LVRPGASVKL
LAASPGETIT
LVRPGASVKL
LAASPGETIT






SCTASGFNIK
INCRASKSIS
SCTASGFNIK
INCRASKSIS






DDYIHWVKQR
KYLAWYQEKP
DDYIHWVKQR
KYLAWYQEKP






PEQGLEWIGR
GKTNKVLIYS
PEQGLEWIGR
GKTNKVLIYS






IDPANGNPRY
GSTLQSGIPS
IDPANGNPRY
GSTLQSGIPS






APKFQDKATL
RFSGSGSGTD
APKFQDKATL
RFSGSGSGTD






TADTSSNTAY
FTLTISSLEP
TADTSSNTAY
FTLTISSLEP






LQLSSLTSED
EDFAIYYCQQ
LQLSSLTSED
EDFAIYYCQQ






TAVYYCARDD
HNEYPLTFGD
TAVYYCARDD
HNEYPLTFGD






EGYYYFDVWG
GTRLEIK
EGYYYFDVWG
GTRLEIKRTV






AGTSVTVSS

AGTSVTVSSA
AAPSVFIFPP








STKGPSVFPL
SDEQLKSGTA








APSSKSTSGG
SVVCLLNNFY








TAALGCLVKD
PREAKVQWKV








YFPEPVTVSW
DNALQSGNSQ








NSGALTSGVH
ESVTEQDSKD








TFPAVLQSSG
STYSLSSTLT








LYSLSSVVTV
LSKADYEKHK








PSSSLGTQTY
VYACEVTHQG








ICNVNHKPSN
LSSPVTKSFN








TKVDKKVEPK
RGEC








SCDKTHTCPP









CPAPELLGGP









SVFLFPPKPK









DTLMISRTPE









VTCVVVDVSH









EDPEVKFNWY









VDGVEVHNAK









TKPREEQYNS









TYRVVSVLTV









LHQDWLNGKE









YKCKVSNKAL









PAPIEKTISK









AKGQPREPQV









YTLPPSREEM









TKNQVSLTCL









VKGFYPSDIA









VEWESNGQPE









NNYKTTPPVL









DSDGSFFLYS









KLTVDKSRWQ









QGNVFSCSVM









HEALHNHYTQ









KSLSLSPGK







1629
1630
1631
1632





49
CD8B368
IgG1
Kappa
QVQLQQPGTE
DIVMTQSQKF
QVQLQQPGTE
DIVMTQSQKF






LVKPGASVKL
MSTTVGDRVS
LVKPGASVKL
MSTTVGDRVS






SCKASGYTFT
ITCKASQNVG
SCKASGYTFT
ITCKASQNVG






SYWINWMKQR
IAVAWFQQKP
SYWINWMKQR
IAVAWFQQKP






PGQGLEWIGN
GQSPKLLIYS
PGQGLEWIGN
GQSPKLLIYS






TYPFSSSTNY
ASNRYTGVPD
IYPFSSSTNY
ASNRYTGVPD






NEKFKKKATL
RFTGSGSGTD
NEKFKKKATL
RFTGSGSGTD






TVDASSSTAS
FTLTIGNMQS
TVDASSSTAS
FTLTIGNMQS






MQLSSLTSDD
EDLADYFCQQ
MQLSSLTSDD
EDLADYFCQQ






SAVYFCAREE
YSTDPYTFGS
SAVYFCAREE
YSTDPYTFGS






FSHYPSWFAY
GTKLEIK
FSHYPSWFAY
GTKLEIKRTV






WGQGTTLTVS

WGQGTTLTVS
AAPSVFIFPP






S

SASTKGPSVF
SDEQLKSGTA








PLAPSSKSTS
SVVCLLNNFY








GGTAALGCLV
PREAKVQWKV








KDYFPEPVTV
DNALQSGNSQ








SWNSGALTSG
ESVTEQDSKD








VHTFPAVLQS
STYSLSSTLT








SGLYSLSSVV
LSKADYEKHK








TVPSSSLGTQ
VYACEVTHQG








TYICNVNHKP
LSSPVTKSFN








SNTKVDKKVE
RGEC








PKSCDKTHTC









PPCPAPELLG









GPSVFLFPPK









PKDTLMISRT









PEVTCVVVDV









SHEDPEVKFN









WYVDGVEVHN









AKTKPREEQY









NSTYRVVSVL









TVLHQDWLNG









KEYKCKVSNK









ALPAPIEKTI









SKAKGQPREP









QVYTLPPSRE









EMTKNQVSLT









CLVKGFYPSD









IAVEWESNGQ









PENNYKTTPP









VLDSDGSFFL









YSKLTVDKSR









WQQGNVFSCS









VMHEALHNHY









TQKSLSLSPG









K







1663
1664
1665
1666





50
CD8B370
IgG1
Kappa
EVQLQQSGAE
DIVLTQSQKI
EVQLQQSGAE
DIVLTQSQKI






LVKPGASVKL
MSTTVGDRVS
LVKPGASVKL
MSTTVGDRVS






SCKASGYTFT
ITCKASQNVG
SCKASGYTFT
ITCKASQNVG






SYWINWVKQR
TAVAWYQQKP
SYWINWVKQR
TAVAWYQQKP






PGQGLEWIGN
GQSPKLLIYS
PGQGLEWIGN
GQSPKLLIYS






IYPGSSSTNY
ASNRYTGVPD
IYPGSSSTNY
ASNRYTGVPD






NEKFKNKATL
RFTGSGSGTD
NEKFKNKATL
RFTGSGSGTD






TVDTSSSTVY
FTLTISNMQS
TVDTSSSTVY
FTLTISNMQS






MQLSSLTSDD
EDLADYFCQQ
MQLSSLTSDD
EDLADYFCQQ






SAVYYCTREL
YSIYPFTFGS
SAVYYCTREL
YSIYPFTFGS






GAYYHYSAMD
GTKLEIK
GAYYHYSAMD
GTKLEIKRTV






YWGQGTSVTV

YWGQGTSVTV
AAPSVFIFPP






SS

SSASTKGPSV
SDEQLKSGTA








FPLAPSSKST
SVVCLLNNFY








SGGTAALGCL
PREAKVQWKV








VKDYFPEPVT
DNALQSGNSQ








VSWNSGALTS
ESVTEQDSKD








GVHTFPAVLQ
STYSLSSTLT








SSGLYSLSSV
LSKADYEKHK








VTVPSSSLGT
VYACEVTHQG








QTYICNVNHK
LSSPVTKSFN








PSNTKVDKKV
RGEC








EPKSCDKTHT









CPPCPAPELL









GGPSVFLFPP









KPKDTLMISR









TPEVTCVVVD









VSHEDPEVKF









NWYVDGVEVH









NAKTKPREEQ









YNSTYRVVSV









LTVLHQDWLN









GKEYKCKVSN









KALPAPIEKT









ISKAKGQPRE









PQVYTLPPSR









EEMTKNQVSL









TCLVKGFYPS









DIAVEWESNG









QPENNYKTTP









PVLDSDGSFF









LYSKLTVDKS









RWQQGNVFSC









SVMHEALHNH









YTQKSLSLSP









GK







1697
1698
1699
1700





51
CD8B186
IgG1
Kappa
QVQLQQSGAE
DVQMIQSPAS
QVQLQQSGAE
DVQMIQSPAS






LAKPGASVKM
LSASVGETVT
LAKPGASVKM
LSASVGETVT






SCKASGYIFT
ITCRASGNIH
SCKASGYIFT
ITCRASGNIH






SYWMHWVKQR
NYLAWYQQKQ
SYWMHWVKQR
NYLAWYQQKQ






PGQGLEWIGN
GKSPQLLVYN
PGQGLEWIGN
GKSPQLLVYN






INPSSGYAVY
AKTLADGVPS
INPSSGYAVY
AKTLADGVPS






NQKFKDKATL
RFSGSGSGTQ
NQKFKDKATL
RFSGSGSGTQ






TADQSSSTAY
YSLKINSLQP
TADQSSSTAY
YSLKINSLQP






IQLNSLTSED
EDFGSYYCQH
IQLNSLTSED
EDFGSYYCQH






SAVYYCARRV
FWSTTWTFGG
SAVYYCARRV
FWSTTWTFGG






FYGDSWFAYW
GTKLEIK
FYGDSWFAYW
GTKLEIKRTV






GQGTSVTVSS

GQGTSVTVSS
AAPSVFIFPP








ASTKGPSVFP
SDEQLKSGTA








LAPSSKSTSG
SVVCLLNNFY








GTAALGCLVK
PREAKVQWKV








DYFPEPVTVS
DNALQSGNSQ








WNSGALTSGV
ESVTEQDSKD








HTFPAVLQSS
STYSLSSTLT








GLYSLSSVVT
LSKADYEKHK








VPSSSLGTQT
VYACEVTHQG








YICNVNHKPS
LSSPVTKSFN








NTKVDKKVEP
RGEC








KSCDKTHTCP









PCPAPELLGG









PSVFLFPPKP









KDTLMISRTP









EVTCVVVDVS









HEDPEVKFNW









YVDGVEVHNA









KTKPREEQYN









STYRVVSVLT









VLHQDWLNGK









EYKCKVSNKA









LPAPIEKTIS









KAKGQPREPQ









VYTLPPSREE









MTKNQVSLTC









LVKGFYPSDI









AVEWESNGQP









ENNYKTTPPV









LDSDGSFFLY









SKLTVDKSRW









QQGNVFSCSV









MHEALHNHYT









QKSLSLSPGK







1731
1732
1733
1734





52
CD8B190
IgG1
Kappa
EFQLQQSGPE
NTQMNQTPSS
EFQLQQSGPE
NTQMNQTPSS






LMKPGASVKI
LSASLGDTVT
LMKPGASVKI
LSASLGDTVT






SCKASGYSFT
ITCHASQNIN
SCKASGYSFT
ITCHASQNIN






SYYMHWMKQS
VWLSWYQQKP
SYYMHWMKQS
VWLSWYQQKP






HGKSLEWIGY
GNIPKLLIYK
HGKSLEWIGY
GNIPKLLIYK






IDPFNGNTNY
ASNLHTGVPS
IDPFNGNTNY
ASNLHTGVPS






KQKFKGKATL
RFSGSGSGTG
KQKFKGKATL
RFSGSGSGTG






TVDKSSSTAY
FTLTISSLQP
TVDKSSSTAY
FTLTISSLQP






MHLSSLTSED
DDIATYYCQQ
MHLSSLTSED
DDIATYYCQQ






SAVYYCASPN
GQSFPFTFGS
SAVYYCASPN
GQSFPFTFGS






SNYVGTWFAY
GTKLEIK
SNYVGTWFAY
GTKLEIKRTV






WGQGTTVTVS

WGQGTTVTVS
AAPSVFIFPP






S

SASTKGPSVF
SDEQLKSGTA








PLAPSSKSTS
SVVCLLNNFY








GGTAALGCLV
PREAKVQWKV








KDYFPEPVTV
DNALQSGNSQ








SWNSGALTSG
ESVTEQDSKD








VHTFPAVLQS
STYSLSSTLT








SGLYSLSSVV
LSKADYEKHK








TVPSSSLGTQ
VYACEVTHQG








TYICNVNHKP
LSSPVTKSFN








SNTKVDKKVE
RGEC








PKSCDKTHTC









PPCPAPELLG









GPSVFLFPPK









PKDTLMISRT









PEVTCVVVDV









SHEDPEVKFN









WYVDGVEVHN









AKTKPREEQY









NSTYRVVSVL









TVLHQDWLNG









KEYKCKVSNK









ALPAPIEKTI









SKAKGQPREP









QVYTLPPSRE









EMTKNQVSLT









CLVKGFYPSD









IAVEWESNGQ









PENNYKTTPP









VLDSDGSFFL









YSKLTVDKSR









WQQGNVFSCS









VMHEALHNHY









TQKSLSLSPG









K







1765
1766
1767
1768





53
CD8B192
IgG1
Kappa
QVQLQQSGPV
DIQMTQSPAS
QVQLQQSGPV
DIQMTQSPAS






LVKPGASVKM
LSASVGETVT
LVKPGASVKM
LSASVGETVT






SCKASGYTFT
ITCRASGNIH
SCKASGYTFT
ITCRASGNIH






DYYMNWVMQS
NYLAWYQQKQ
DYYMNWVMQS
NYLAWYQQKQ






HGKSLEWIGV
GKSPQLLVSN
HGKSLEWIGV
GKSPQLLVSN






INPYNGGTTY
AKTLADGVPS
INPYNGGTTY
AKTLADGVPS






NQRFTGKATL
RFGGSGSGTQ
NQRFTGKATL
RFGGSGSGTQ






TVDKSSS
YSLKINSLQP
TVDKSSSTAY
YSLKINSLQP






TAYMELNSLT
EDFGSYYCQH
MELNSLTSED
EDFGSYYCQH






SEDSAVYYCA
FWITPPTFGA
SAVYYCARNY
FWITPPTFGA






RNYGAMDSWG
GTRLEIK
GAMDSWGQGT
GTRLEIKRTV






QGTSVTVSS

SVTVSSASTK
AAPSVFIFPP








GPSVFPLAPS
SDEQLKSGTA








SKSTSGGTAA
SVVCLLNNFY








LGCLVKDYFP
PREAKVQWKV








EPVTVSWNSG
DNALQSGNSQ








ALTSGVHTFP
ESVTEQDSKD








AVLQSSGLYS
STYSLSSTLT








LSSVVTVPSS
LSKADYEKHK








SLGTQTYICN
VYACEVTHQG








VNHKPSNTKV
LSSPVTKSFN








DKKVEPKSCD
RGEC








KTHTCPPCPA









PELLGGPSVF









LFPPKPKDTL









MISRTPEVT









CVVVDVSHED









PEVKFNWYVD









GVEVHNAKTK









PREEQYNSTY









RVVSVLTVLH









QDWLNGKEYK









CKVSNKALPA









PIEKTISKAK









GQPREPQVYT









LPPSREEMTK









NQVSLTCLVK









GFYPSDIAVE









WESNGQPENN









YKTTPPVLDS









DGSFFLYSKL









TVDKSRWQQG









NVFSCSVMHE









ALHNHYTQKS









LSLSPGK







1799
1800
1801
1802





54
CD8B193
IgG1
Kappa
DVQLQESGPE
DIVMTQSQKF
DVQLQESGPE
DIVMTQSQKF






LVKPGASVKI
MSTTVGDRVS
LVKPGASVKI
MSTTVGDRVS






ACKTSGYKFT
ITCKASQNVG
ACKTSGYKFT
ITCKASQNVG






DYYMNWVKQS
TAVAWYQQKP
DYYMNWVKQS
TAVAWYQQKP






LGKSLDWIGD
GQSPKLLIYS
LGKSLDWIGD
GQSPKLLIYS






INPNGGGTSD
ASNRYTGVPD
INPNGGGTSD
ASNRYTGVPD






NPKFKGKATL
RFTGSGSGTD
NPKFKGKATL
RFTGSGSGTD






TVDKSSSTAY
FTLTISNMQS
TVDKSSSTAY
FTLTISNMQS






MELRSLTSED
EDLADYFCQQ
MELRSLTSED
EDLADYFCQQ






SGVYYCARTS
YSSYPFTFGS
SGVYYCARTS
YSSYPFTFGS






GTDWYFDVWG
GTKLEMK
GTDWYFDVWG
GTKLEMKRTV






TGTTVTVSS

TGTTVTVSSA
AAPSVFIFPP








STKGPSVFPL
SDEQLKSGTA








APSSKSTSGG
SVVCLLNNFY








TAALGCLVKD
PREAKVQWKV








YFPEPVTVSW
DNALQSGNSQ








NSGALTSGVH
ESVTEQDSKD








TFPAVLQSSG
STYSLSSTLT








LYSLSSVVTV
LSKADYEKHK








PSSSLGTQTY
VYACEVTHQG








ICNVNHKPSN
LSSPVTKSFN








TKVDKKVEPK
RGEC








SCDKTHTCPP









CPAPELLGGP









SVFLFPPKPK









DTLMISRTPE









VTCVVVDVSH









EDPEVKFNWY









VDGVEVHNAK









TKPREEQYNS









TYRVVSVLTV









LHQDWLNGKE









YKCKVSNKAL









PAPIEKTISK









AKGQPREPQV









YTLPPSREEM









TKNQVSLTCL









VKGFYPSDIA









VEWESNGQPE









NNYKTTPPVL









DSDGSFFLYS









KLTVDKSRWQ









QGNVFSCSVM









HEALHNHYTQ









KSLSLSPGK







1833
1834
1835
1836





55
CD8B214
IgG1
Kappa
QVQLQQSGPE
DIQMTQTTSS
QVQLQQSGPE
DIQMTQTTSS






LKKPGETVKI
LSASLGDRVT
LKKPGETVKI
LSASLGDRVT






SCKASGYTFT
ITCRASQDIR
SCKASGYTFT
ITCRASQDIR






TAGIQWVQKM
PYLNWYQQKP
TAGIQWVQKM
PYLNWYQQKP






PGKGFKWIGW
EGTIKLLIYY
PGKGFKWIGW
EGTIKLLIYY






INTHAGESKY
TSRLHSGVPS
INTHAGESKY
TSRLHSGVPS






ADDFKGRFAV
RFSGSGSGTD
ADDFKGRFAV
RFSGSGSGTD






SLETSASTAY
YSLTISNLEQ
SLETSASTAY
YSLTISNLEQ






LQISNLKNED
EDIATYFCQQ
LQISNLKNED
EDIATYFCQQ






TATYFCARSG
DNTLPYTFGS
TATYFCARSG
DNTLPYTFGS






DYDGSHPFAY
GTKLEIK
DYDGSHPFAY
GTKLEIKRTV






WGQGTSVTVS

WGQGTSVTVS
AAPSVFIFPP






S

SASTKGPSVF
SDEQLKSGTA








PLAPSSKSTS
SVVCLLNNFY








GGTAALGCLV
PREAKVQWKV








KDYFPEPVTV
DNALQSGNSQ








SWNSGALTSG
ESVTEQDSKD








VHTFPAVLQS
STYSLSSTLT








SGLYSLSSVV
LSKADYEKHK








TVPSSSLGTQ
VYACEVTHQG








TYICNVNHKP
LSSPVTKSFN








SNTKVDKKVE
RGEC








PKSCDKTHTC









PPCPAPELLG









GPSVFLFPPK









PKDTLMISRT









PEVTCVVVDV









SHEDPEVKFN









WYVDGVEVHN









AKTKPREEQY









NSTYRVVSVL









TVLHQDWLNG









KEYKCKVSNK









ALPAPIEKTI









SKAKGQPREP









QVYTLPPSRE









EMTKNQVSLT









CLVKGFYPSD









IAVEWESNGQ









PENNYKTTPP









VLDSDGSFFL









YSKLTVDKSR









WQQGNVFSCS









VMHEALHNHY









TQKSLSLSPG









K







1867
1868
1869
1870





56
CD8B230
IgG1
Kappa
QIQLVQSGPE
DIVMTQSQKF
QIQLVQSGPE
DIVMTQSQKF






LVKPGASVKI
MSTTVGDRVS
LVKPGASVKI
MSTTVGDRVS






SCKASGYTFT
ITCKASQNVG
SCKASGYTFT
ITCKASQNVG






DYYMNWVKQS
TAVAWYQQKP
DYYMNWVKQS
TAVAWYQQKP






HGKS
GQSPKLLIYS
HGKSLDWIGD
GQSPKLLIYS






LDWIGDINPN
TSNRYTGVPD
INPNGGGTSD
TSNRYTGVPD






GGGTSDNPKF
RFTGSGSGTD
NPKFKGKATL
RFTGSGSGTD






KGKATLTVDK
FTLTISNMQS
TVDKSSNTAY
FTLTISNMQS






SSNTAYMELR
EDLADYFCQQ
MELRSLTSED
EDLADYFCQQ






SLTSEDSAVY
YSIYPFTFGS
SAVYYCARTS
YSIYPFTFGS






YCARTSGTDW
GTKLEMK
GTDWYFDVWG
GTKLEMKRTV






YFDVWGTGTL

TGTLVTVSAA
AAPSVFIFPP






VTVSA

STKGPSVFPL
SDEQLKSGTA








APSSKSTSGG
SVVCLLNNFY








TAALGCLV
PREAKVQWKV








KDYFPEPVTV
DNALQSGNSQ








SWNSGALTSG
ESVTEQDSKD








VHTFPAVLQS
STYSLSSTLT








SGLYSLSSVV
LSKADYEKHK








TVPSSSLGTQ
VYACEVTHQG








TYICNVNHKP
LSSPVTKSFN








SNTKVDKKVE
RGEC








PKSCDKTHTC









PPCPAPELLG









GPSVFLFPPK









PKDTLMISRT









PEVTCVVVDV









SHEDPEVKFN









WYVDGVEVHN









AKTKPREEQY









NSTYRVVSVL









TVLHQDWLNG









KEYKCKVSNK









ALPAPIEKTI









SKAKGQPREP









QVYTLPPSRE









EMTKNQVSLT









CLVKGFYPSD









IAVEWESNGQ









PENNYKTTPP









VLDSDGSFFL









YSKLTVDKSR









WQQGNVFSCS









VMHEALHNHY









TQKSLSLSPG









K







1901
1902
1903
1904





57
CD8B245
IgG1
Kappa
EFQLQQSGGG
DIQMTQSPAS
EFQLQQSGGG
DIQMTQSPAS






LVQPGGSLSL
LSASVGETVT
LVQPGGSLSL
LSASVGETVT






SCAAPGFTFT
ITCRASENIY
SCAAPGFTFT
ITCRASENIY






DYYMSWVRQS
SYLAWYQQKQ
DYYMSWVRQS
SYLAWYQQKQ






PGKALEWLAL
GKSPQFLVYN
PGKALEWLAL
GKSPQFLVYN






SRNKGNGYTT
AKTLAAGVPS
SRNKGNGYTT
AKTLAAGVPS






EYSASVKGRF
RFSGSGSGTQ
EYSASVKGRF
RFSGSGSGTQ






TISRDNSQSI
FSLKINRLQP
TISRDNSQSI
FSLKINRLQP






LYLQMNVLRA
EDFGTYYCQH
LYLQMNVLRA
EDFGTYYCQH






EDSATYYCAR
HYGTPLTFGD
EDSATYYCAR
HYGTPLTFGD






TVTGTLFYYA
GTRLEIK
TVTGTLFYYA
GTRLEIKRTV






LDYWGQGTTV

LDYWGQGTTV
AAPSVFIFPP






TVSS

TVSSASTKGP
SDEQLKSGTA








SVFPLAPSSK
SVVCLLNNFY








STSGGTAALG
PREAKVQWKV








CLVKDYFPEP
DNALQSGNSQ








VTVSWNSGAL
ESVTEQDSKD








TSGVHTFPAV
STYSLSSTLT








LQSSGLYSLS
LSKADYEKHK








SVVTVPSSSL
VYACEVTHQG








GTQTYICNVN
LSSPVTKSFN








HKPSNTKVDK
RGEC








KVEPKSCDKT









HTCPPCPAPE









LLGGPSVFLF









PPKPKDTLMI









SRTPEVTCVV









VDVSHEDPEV









KFNWYVDGVE









VHNAKTKPRE









EQYNSTYRVV









SVLTVLHQDW









LNGKEYKCKV









SNKALPAPIE









KTISKAKGQP









REPQVYTLPP









SREEMTKNQV









SLTCLVKGFY









PSDIAVEWES









NGQPENNYKT









TPPVLDSDGS









FFLYSKLTVD









KSRWQQGNVF









SCSVMHEALH









NHYTQKSLSL









SPGK







1935
1936
1937
1938





58
CD8B248
IgG1
Kappa
EVQLQQSGAE
DWMTQTPLSL
EVQLQQSGAE
DWMTQTPLSL






LARPGASVKM
PVSLGDQASI
LARPGASVKM
PVSLGDQASI






SCKASGYTFT
SCRSSQSLVH
SCKASGYTFT
SCRSSQSLVH






TYTMHWVKQR
SSGNTYLHWY
TYTMHWVKQR
SSGNTYLHWY






PGQGLEWIGY
LQKPGQSPKL
PGQGLEWIGY
LQKPGQSPKL






INPSSGYTKY
LIYKGSNRFS
INPSSGYTKY
LIYKGSNRFS






NQKFTDKATL
GVSDRFSGSG
NQKFTDKATL
GVSDRFSGSG






TADKSSSTAY
SGTDFTLKIS
TADKSSSTAY
SGTDFTLKIS






MQLSSLTSED
RVEAEDLGVY
MQLSSLTSED
RVEAEDLGVY






SAVYYCARLW
FCSQSTHVPF
SAVYYCARLW
FCSQSTHVPF






AYWGQGTLVT
TFGSGTKLEM
AYWGQGTLVT
TFGSGTKLEM






VSA
K
VSAASTKGPS
KRTVAAPSVF








VFPLAPSSKS
IFPPSDEQLK








TSGGTAALGC
SGTASVVCLL








LVKDYFPEPV
NNFYPREAKV








TVSWNSGALT
QWKVDNALQS








SGVHTFPAVL
GNSQESVTEQ








QSSGLYSLSS
DSKDSTYSLS








VVTVPSSSLG
STLTLSKADY








TQTYICNVNH
EKHKVYACEV








KPSNTKVDKK
THQGLSSPVT








VEPKSCDKTH
KSFNRGEC








TCPPCPAPEL









LGGPSVFLFP









PKPKDTLMIS









RTPEVTCVVV









DVSHEDPEVK









FNWYVDGVEV









HNAKTKPREE









QYNSTYRVVS









VLTVLHQDWL









NGKEYKCKVS









NKALPAPIEK









TISKAKGQPR









EPQVYTLPPS









REEMTKNQVS









LTCLVKGFYP









SDIAVEWESN









GQPENNYKTT









PPVLDSDGSF









FLYSKLTVDK









SRWQQGNVFS









CSVMHEALHN









HYTQKSLSLS









PGK







1969
1970
1971
1972





59
CD8B250
IgG1
Kappa
QVQLKESGPGL
DIVMTQSQKF
QVQLKESGPG
DIVMTQSQKF






VAPSQSLSITC
MSTSVGDRVS
LVAPSQSLSI
MSTSVGDRVS






TVSGFSLSNY
VTCKASQNVD
TCTVSGFSLS
VTCKASQNVD






VVHWVRQSPG
TDITWYQQKP
NYWHWVRQSP
TDITWYQQKP






KGLEWLGVIW
GQSPKALIYS
GKGLEWLGVI
GQSPKALIYS






TDGSTDYNAA
ASYRYSGVPD
WTDGSTDYNA
ASYRYSGVPD






FISRLSISKD
RFTGSGSGTD
AFISRLSISK
RFTGSGSGTD






NSKSQVFFKM
FTLTITNVQS
DNS
FTLTITNVQS






NSLQADDTAI
EDLAEYFCQQ
KSQVFFKMNS
EDLAEYFCQQ






YYCARNNGYF
YNSYPLTFGS
LQADDTAIYY
YNSYPLTFGS






PAFFAYWGQG
GTKLEMK
CARNNGYFPA
GTKLEMKRTV






TLVTVSA

FFAYWGQGTL
AAPSVFIFPP








VTVSAASTKG
SDEQLKSGTA








PSVFPLAPSS
SVVCLLNNFY








KSTSGGTAAL
PREAKVQWKV








GCLVKDYFPE
DNALQSGNSQ








PVTVSWNSGA
ESVTEQDSKD








LTSGVHTFPA
STYSLSSTLT








VLQSSGLYSL
LSKADYEKHK








SSVVTVPSSS
VYACEVTHQG








LGTQTYICNV
LSSPVTKSFN








NHKPSNTKVD
RGEC








KKVEPKSCDK









THTCPPCPAP









ELLGGPSVFL









FPPKPKDTLM









ISRTPEVTCV









VVDVSHEDPE









VKFNWYVDGV









EVHNAKTKPR









EEQYNSTYRV









VSVLTVLHQD









WLNGKEYKCK









VSNKALPAPI









EKTISKAKGQ









PREPQVYTLP









PSREEMTKNQ









VSLTCLVKGF









YPSDIAVEWE









SNGQPENNYK









TTPPVLDSDG









SFFLYSKLTV









DKSRWQQGNV









FSCSVMHEAL









HNHYTQKSLS









LSPGK







2003
2004
2005
2006





60
CD8B254
IgG1
Kappa
EVQLQQSGAE
DWMTQTPLSL
EVQLQQSGAE
DVVMTQTPLS






LVKPGASVKM
PVSLGDQASI
LVKPGASVKM
LPVSLGDQAS






SCKTSGYTFS
SCRSSQSLVH
SCKTSGYTFS
ISCRSSQSLV






SYWITWVKQR
SSGNTYLHWY
SYWITWVKQR
HSSGNTYLHW






PGQGLEWVGD
LQKPGQSPKL
PGQGLEWVGD
YLQKPGQSPK






IYPGSGSTNY
LIYKGSNRFS
IYPGSGSTNY
LLIYKGSNRF






NEKFKSKAAL
GVSDRFSGSG
NEKFKSKAAL
SGVSDRFSGS






TVDTSSSTAF
SGTDFTLKIS
TVDTSSSTAF
GSGTDFTLKI






MQLNSLTSED
RVEAEDLGVY
MQLNSLTSED
SRVEAEDLGV






SAVYYCARES
FCSQSTHVPF
SAVYYCARES
YFCSQSTHVP






ITTRITPFDH
TFGSGTKLEI
ITTRITPFDH
FTFGSGTKLE






WGQGTTLTVS
K
WGQGTTLTVS
IKRTVAAPSV






S

SASTKGPSVF
FIFPPSDEQL








PLAPSSKSTS
KSGTASVVCL








GGTAALGCLV
LNNFYPREAK








KDYFPEPVTV
VQWKVDNALQ








SWNSGALTSG
SGNSQESVTE








VHTFPAVLQS
QDSKDSTYSL








SGLYSLSSVV
SSTLTLSKAD








TVPSSSLGTQ
YEKHKVYACE








TYICNVNHKP
VTHQGLSSPV








SNTKVDKKVE
TKSFNRGEC








PKSCDKTHTC









PPCPAPELLG









GPSVFLFPPK









PKDTLMISRT









PEVTCVVVDV









SHEDPEVKFN









WYVDGVEVHN









AKTKPREEQY









NSTYRVVSVL









TVLHQDWLNG









KEYKCKVSNK









ALPAPIEKTI









SKAKGQPREP









QVYTLPPSRE









EMTKNQVSLT









CLVKGFYPSD









IAVEWESNGQ









PENNYKTTPP









VLDSDGSFFL









YSKLTVDKSR









WQQGNVFSCS









VMHEALHNHY









TQKSLSLSPG









K







2037
2038
2039
2040





61
CD8B261
IgG1
Kappa
QVQLQQPGAE
DIVLTQSPSS
QVQLQQPGAE
DIVLTQSPSS






LVKPGASVKL
MYASLGERVT
LVKPGASVKL
MYASLGERVT






SCKASGYTFN
ITCKASQDIN
SCKASGYTFN
ITCKASQDIN






SYWINWMKQR
RYLSWFQQKP
SYWINWMKQR
RYLSWFQQKP






PGQGLEWIGN
GKSPKTLIYR
PGQGLEWIGN
GKSPKTLIYR






IYPGSSSTNY
ANTLVDGVPS
IYPGSSSTNY
ANTLVDGVPS






NEKFKSKATL
RFSGSGSGQD
NEKFKSKATL
RFSGSGSGQD






TVDTSSSTAY
YSLTISSLEY
TVDTSSSTAY
YSLTISSLEY






MQLSSLTSDD
EDMGIYYCLQ
MQLSSLTSDD
EDMGIYYCLQ






SAVYYCAREL
YDEFPYTFGS
SAVYYCAREL
YDEFPYTFGS






GGYYRYNAMD
GTKLEMK
GGYYRYNAMD
GTKLEMKRTV






YWGQGTSVTV

YWGQGTSVTV
AAPSVFIFPP






SS

SSASTKGPSV
SDEQLKSGTA








FPLAPSSKST
SVVCLLNNFY








SGGTAALGCL
PREAKVQWKV








VKDYFPEPVT
DNALQSGNSQ








VSWNSGALTS
ESVTEQDSKD








GVHTFPAVLQ
STYSLSSTLT








SSGLYSLSSV
LSKADYEKHK








VTVPSSSLGT
VYACEVTHQG








QTYICNVNHK
LSSPVTKSFN








PSNTKVDKKV
RGEC








EPKSCDKTHT









CPPCPAPELL









GGPSVFLFPP









KPKDTLMISR









TPEVTCVVVD









VSHEDPEVKF









NWYVDGVEVH









NAKTKPREEQ









YNSTYRVVSV









LTVLHQDWLN









GKEYKCKVSN









KALPAPIEKT









ISKAKGQPRE









PQVYTLPPSR









EEMTKNQVSL









TCLVKGFYPS









DIAVEWESNG









QPENNYKTTP









PVLDSDGSFF









LYSKLTVDKS









RWQQGNVFSC









SVMHEALHNH









YTQKSLSLSP









GK







2071
2072
2073
2074





62
CD8B311
IgG1
Kappa
QVQLKESGPE
DIQMTQTTSS
QVQLKESGPE
DIQMTQTTSS






LVKPGASVKL
LSASLGDRVT
LVKPGASVKL
LSASLGDRVT






SCKASGYTFT
ISCSASQGIS
SCKASGYTFT
ISCSASQGIS






SYWMHWVKQR
NCLNWYQQKP
SYWMHWVKQR
NCLNWYQQKP






PGQGLEWIGM
DGTVKLLIHY
PGQGLEWIGM
DGTVKLLIHY






IHPNSGSTNY
TSSLHSGVPS
IHPNSGSTNY
TSSLHSGVPS






NEKFKSKATL
RFSGGGSGTH
NEKFKSKATL
RFSGGGSGTH






TVDKSSSTAY
YSLTISNLEP
TVDKSSSTAY
YSLTISNLEP






MQLSSLTSED
EDIATYYCQQ
MQLSSLTSED
EDIATYYCQQ






SAVYYCARCG
YSKVPYTFGS
SAVYYCARCG
YSKVPYTFGS






YDGAWFAYWG
GTKLEIK
YDGAWFAYWG
GTKLEIKRTV






QGTSVTVSS

QGTSVTVSSA
AAPSVFIFPP








STKGPSVFPL
SDEQLKSGTA








APSSKSTSGG
SVVCLLNNFY








TAALGCLVKD
PREAKVQWKV








YFPEPVTVSW
DNALQSGNSQ








NSGALTSGVH
ESVTEQDSKD








TFPAVLQSSG
STYSLSSTLT








LYSLSSVVTV
LSKADYEKHK








PSSSLGTQTY
VYACEVTHQG








ICNVNHKPSN
LSSPVTKSFN








TKVDKKVEPK
RGEC








SCDKTHTCPP









CPAPELLGGP









SVFLFPPKPK









DTLMISRTPE









VTCVVVDVSH









EDPEVKFNWY









VDGVEVHNAK









TKPREEQYNS









TYRVVSVLTV









LHQDWLNGKE









YKCKVSNKAL









PAPIEKTISK









AKGQPREPQV









YTLPPSREEM









TKNQVSLTCL









VKGFYPSDIA









VEWESNGQPE









NNYKTTPPVL









DSDGSFFLYS









KLTVDKSRWQ









QGNVFSCSVM









HEALHNHYTQ









KSLSLSPGK







2105
2106
2107
2108





63
CD8B340
IgG1
Kappa
QVQLQQPGAE
DIVMTQTPLT
QVQLQQPGAE
DIVMTQTPLT






LVKPGASVRL
LSVTIGQPAS
LVKPGASVRL
LSVTIGQPAS






SCKASGYTFT
ISCKSSQSLL
SCKASGYTFT
ISCKSSQSLL






NYWMQWVQQR
YSDGKTYLNW
NYWMQWVQQR
YSDGKTYLNW






PGQGLEWIGE
LLQRPGESPK
PGQGLEWIGE
LLQRPGESPK






IDPSDTFTNY
LLIYLVSKLD
IDPSDTFTNY
LLIYLVSKLD






NQNFKDKATL
SGVPDRFTGS
NQNFKDKATL
SGVPDRFTGS






TVDTSSSTAY
GSGTDFTLKI
TVDTSSSTAY
GSGTDFTLKI






LQLSSLTSED
SRVETEDLGI
LQLSSLTSED
SRVETEDLGI






SAVYYCARGD
YYCLQATHFP
SAVYYCARGD
YYCLQATHFP






WDRDWYFDVW
HTFGAGTKLE
WDRDWYFDVW
HTFGAGTKLE






GTGTLVTVSA
LK
GTGTLVTVSA
LKRTVAAPSV








ASTKGPSVFP
FIFPPSDEQL








LAPSSKSTSG
KSGTASVVCL








GTAALGCLVK
LNNFYPREAK








DYFPEPVTVS
VQWKVDNALQ








WNSGALTSGV
SGNSQESVTE








HTFPAVLQSS
QDSKDSTYSL








GLYSLSSVVT
SSTLTLSKAD








VPSSSLGTQT
YEKHKVYACE








YICNVNHKPS
VTHQGLSSPV








NTKVDKKVEP
TKSFNRGEC








KSCDKTHTCP









PCPAPELLGG









PSVFLFPPKP









KDTLMISRTP









EVTCVVVDVS









HEDPEVKFNW









YVDGVEVHNA









KTKPREEQYN









STYRVVSVLT









VLHQDWLNGK









EYKCKVSNKA









LPAPIEKTIS









KAKGQPREPQ









VYTLPPSREE









MTKNQVSLTC









LVKGFYPSDI









AVEWESNGQP









ENNYKTTPPV









LDSDGSFFLY









SKLTVDKSRW









QQGNVFSCSV









MHEALHNHYT









QKSLSLSPGK







2139
2140
2141
2142





64
CD8B362
IgG1
Kappa
EVKLVESGAE
DIQMTQSPSS
EVKLVESGAE
DIQMTQSPSS






LVKPGASVKL
LSASLGDRVS
LVKPGASVKL
LSASLGDRVS






SCTASGFNIK
LTCRASHEIS
SCTASGFNIK
LTCRASHEIS






DTYMHWVKQR
GYLSWLQQKP
DTYMHWVKQR
GYLSWLQQKP






PEQGLEWIGR
DGTFKRLIYA
PEQGLEWIGR
DGTFKRLIYA






IDPANGHTKF
ASTLDSGVPK
IDPANGHTKF
ASTLDSGVPK






DPKFQGKATI
RFSGSRSGSD
DPKFQGKATI
RFSGSRSGSD






TADTSSNTAY
YSLSISSLES
TADTSSNTAY
YSLSISSLES






LQLSSLTSED
EDFADYYCLQ
LQLSSLTSED
EDFADYYCLQ






TAVYYCAIRF
YSSYPYTFGS
TAVYYCAIRF
YSSYPYTFGS






AYWGQGTLVT
GTKLEMK
AYWGQGTLVT
GTKLEMKRTV






VSA

VSAASTKGPS
AAPSVFIFPP








VFPLAPSSKS
SDEQLKSGTA








TSGGTAALGC
SVVCLLNNFY








LVKDYFPEPV
PREAKVQWKV








TVSWNSGALT
DNALQSGNSQ








SGVHTFPAVL
ESVTEQDSKD








QSSGLYSLSS
STYSLSSTLT








VVTVPSSSLG
LSKADYEKHK








TQTYICNVNH
VYACEVTHQG








KPSNTKVDKK
LSSPVTKSFN








VEPKSCDKTH
RGEC








TCPPCPAPEL









LGGPSVFLFP









PKPKDTLMIS









RTPEVTCVVV









DVSHEDPEVK









FNWYVDGVEV









HNAKTKPREE









QYNSTYRVVS









VLTVLHQDWL









NGKEYKCKVS









NKALPAPIEK









TISKAKGQPR









EPQVYTLPPS









REEMTKNQVS









LTCLVKGFYP









SDIAVEWESN









GQPENNYKTT









PPVLDSDGSF









FLYSKLTVDK









SRWQQGNVFS









CSVMHEALHN









HYTQKSLSLS









PGK







2173
2174
2175
2176
















TABLE 3







Kabat CDR Amino Acid Sequences of CD8 Antibodies
















HC



LC




Protein
Kabat


LC Kabat
Kabat
LC Kabat


#
Name
CDR1
HC Kabat CDR2
HC Kabat CDR3
CDR1
CDR2
CDR3

















1
CD8B191
DYYMN
RVIPSNGGTIYNLKFKG
EDYNNQGFFLDAMDY
RASQSISDFLH
YASQSIS
QNGHSFPYT




   1
   2
   3
   4
   5
   6





2
CD8B226
DYYMN
RIIPSNGATIYNQKFKG
EDYSNQGFFLDAMDY
RASQSISHYLH
YASQSIS
QNGHSFPYT




  35
  36
  37
  38
  39
  40





3
CD8B259
DYYMN
RVIPSNGGTIYNQKFRG
EDYGNQGFFLDAMDY
RASQSISHFLH
YASQSIS
QSGHSFPYT




  69
  70
  71
  72
  73
  74





4
CD8B298
DYYMN
RVIPNNGGTRYNQKFKG
EDFSNQGFFLDAMDY
RASQTISDYLH
YASQSIS
QNGHSFPYT




 103
 104
 105
 106
 107
 108





5
CD8B342
DYYVN
RVIPNNGNVIYNQNFKG
EDYSNQGFFLDAMDY
RASQTISNYLH
YASQSIS
QNGHSFPYT




 137
 138
 139
 140
 141
 142





6
CD8B364
SYWMH
EINPSNGDSYYNEKFKR
SMYYDGRAGAY
ITSTDIDDDMN
EGNTLRP
LQSDNMPLT




 171
 172
 173
 174
 175
 176





7
CD8B200
NYWIH
NIDPSDSETHYNQKFKD
GLTGTGYY
RASQDISPYLN
YTSKLHS
QQDNTLPYT




 205
 206
 207
 208
 209
 210





8
CD8B247
DYYMN
RVIPNNGGTIYNQKFKD
EDYSNQGFFLDAMDY
RASQTISHFLH
YASQSIS
QSGHSFPYT




 239
 240
 241
 242
 243
 244





9
CD8B265
DYYMN
RVIPRNGATTYNQNFRG
EDFSNQGFFLDAMDY
RASQSISHYLH
YASQSIS
QNGHSFPYT




 273
 274
 275
 276
 277
 278





10
CD8B270
NYWMH
NIDPSDSETHYNQKFKD
GLTGTGYY
RASQDIRPYLN
FTSKLHS
QQDNTLPYT




 307
 308
 309
 310
 311
 312





11
CD8B213
DYYMD
YIYPNNGITSYNQKFKG
SIYYDHGGGFPY
KASQNVDKYVA
SASYRYS
QQYNTYPS




 341
 342
 343
 344
 345
 346





12
CD8B240
DYYMN
RVIPSNGGTIYNLKFKG
EDYNNQGFFLDAMDY
RASQSISDFLH
YASQSIS
QNGHSFPYT




 375
 376
 377
 378
 379
 380





13
CD8B361
DYYMD
YIYPNNGDTRYNQKFKD
SIYYDHGGGFPY
KASQNVGTYVA
SASYRYS
QQYNSYPT




 409
 410
 411
 412
 413
 414





14
CD8B246
TSGMNVG
HIWWDDDKYYNPSLKS
RGNYGNYEFAY
RASQDIRNYLN
HTSRLHS
QQGNTLPWT




 443
 444
 445
 446
 447
 448





15
CD8B268
VYTIH
WFYPGSGNIKYNEKFKD
HEDNHYYDGNSWFAY
RASGNIHNYLA
NAKTLAD
QHFWNTPYT




 477
 478
 479
 480
 481
 482





16
CD8B271
IYSIH
MIWGGGDTDYNSALKS
NPHYYGGTYEYFDV
SASQGISNYLN
DTSILYS
QQYSNLPYT




 511
 512
 513
 514
 515
 516





17
CD8B273
EYTIH
WFYPGTGSIKYNEKFKD
HEDNHYYDGNSWFAY
RASGNIHNYLA
NAKTLAD
QHFWSTPYT




 545
 546
 547
 548
 549
 550





18
CD8B288
EYTIH
WFYPGNGNMRYNEKFKD
YEDNHYYDGASWFAY
RASGNIHNYLA
NAKTLAD
QHFWSTPFT




 579
 580
 581
 582
 583
 584





19
CD8B292
DDYIY
WIDPENGATEYASKFQG
HDYGYAMDY
TASSSVSSSYLH
STSNLAS
HQYHRSPLT




 613
 614
 615
 616
 617
 618





20
CD8B303
IYSIH
MIWGGGSTDYNSTLNS
NPHHYGGSTGAMDY
KASQDIKKYMA
YTSSLQP
LQYDNLFT




 647
 648
 649
 650
 651
 652





21
CD8B304
TSGMNVG
HIWWDDDKYYNPSLKS
RGNYGNYEFAY
RASQDIRNYLN
HTSRLHS
QQGNTLPWT




 681
 682
 683
 684
 685
 686





22
CD8B312
SFWMH
NVDPSDSQTHYNQKFKD
STYYRYDGPFTY
RASQSINNNLH
YTSQSIS
QQSNSWPLT




 715
 716
 717
 718
 719
 720





23
CD8B347
SYWMN
AVNPSNSYTEYAQKFKD
SGLYNTNHLAWFAY
RASGNIHNYLA
NAETLAD
QHFWNNPLT




 749
 750
 751
 752
 753
 754





24
CD8B350
AYWIN
SINPSNGYTEYSQKFKD
SGLYYTNHLAWCPY
RASGNIHNYLA
NAETLAD
QHFWNSPLT




 783
 784
 785
 786
 787
 788





25
CD8B356
SGYYWN
YISYDGSNNYNPSLKN
NHGDAMDY
KASQNVGTAVA
SASYRYT
QQYSSYLT




 817
 818
 819
 820
 821
 822





26
CD8B369
NTYIS
WIYTGTGGTWYNQKFTD
TNWDWYFDV
RASENIYSYLA
YAKTLTD
QHHYGRPYT




 851
 852
 853
 854
 855
 856





27
CD8B371
DYYMA
HINYDGSITYYLDSLKS
EDYSNYGFAY
HASQNINVWLS
KASNLHT
QQGQSYPLT




 885
 986
 887
 888
 889
 890





28
CD8B182
SYWMN
AVNPTNYYTEYIQKFKD
SGLYNTNHLAWFAY
RASENIHNYLA
NAKTLAN
QHFWTTPLT




 919
 920
 921
 922
 923
 924





29
CD8B205
SYWMH
NIDPSDSETHYNQKFKD
VYYSYYSYDATYFDY
RASENIYSYLA
NAKTLAE
QHHYTTPLT




 953
 954
 955
 956
 957
 958





30
CD8B223
SYSVH
VIWAGGSTNYNSAFMS
HSYYSFDAFDY
KASQNVNTDVA
SASYRYS
QQCNSYPLT




 987
 988
 989
 990
 991
 992





31
CD8B234
SGYYWN
YINYDGRNNYNPSLKN
DQGYSKFYFDY
KASEDIYNRLA
GATSLET
QQYWSFPRT




1021
1022
1023
1024
1025
1026





32
CD8B251
TYAVH
VIWSGGSTDYNAAFIS
HSYYHYNAMDN
KASQNVGTAVA
SASNRYT
QQYSSYPFT




1055
1056
1057
1058
1059
1060





33
CD8B269
SGYYWN
YISYDGSNNYNPSLKN
NHGDAMDH
KASQNVGTDVA
SASYRYS
QQYKSYPLT




1089
1090
1091
1092
1093
1094





34
CD8B290
RYSVH
MIWGGGSTDYNSALKS
IYFDNYVGFAY
KASQDVGTWA
WTSTRHT
QQYSSYPYT




1123
1124
1125
1126
1127
1128





35
CD8B310
NYAVH
VIWTDGSTDYNAGFIS
NNGYFPAFFAY
RSSQTIVHSNGNTYLE
KVSNRFS
FQGSHAPFT




1157
1158
1159
1160
1161
1162





36
CD8B352
SGYYWN
YINYDGRNNYNPSLRN
DQGYSKFYFDY
KASEDIYNRLA
GATSLET
QQYWSFPRT




11S1
1192
1193
1194
1195
1196





37
CD8B319
AYYMH
EINPSAGGTTYNQKFKA
WTNPFDY
KASQNVGTAVA
SASYRYT
QQYNNYLT




1225
1226
1227
1228
1229
1230





38
CD8B194
SYWIN
NIYPGSSSTNYNEKFKS
ELGPYYRYSAMVY
KASQNVGTAVA
SASNRYT
QQYSSYPFT




1259
1260
1261
1262
1263
1264





39
CD8B231
NYWMH
NIDPSDSETHYNQKFKD
GLTGTGHY
RASQDINIYLN
HTSRLHS
QQDNTLPYT




1293
1294
1295
1296
1297
1298





40
CD8B238
DYSMD
YIYTYSGGAGYNRKFKS
DSSDYEFAY
KASQDIKSYLS
RANRLVD
LQYDEFRT




1327
1328
1329
1330
1331
1332





41
CD8B255
TSGMGVS
HIFWDDDKRYNPSLKS
RDGYGDYAYFDV
RASENIYSDLA
AATILTD
QHFWGTPWT




1361
1362
1363
1364
1365
1366





42
CD8B324
SHWIH
NIYPGSSSTNYNEKFKR
HSPGHRDYAMDY
KASQNVGTAVA
SASNRYT
QQYSTYPLT




1395
1396
1397
1398
1399
1400





43
CD8B337
TSGMGVS
HIFWDDDRRYKSSLKS
RVGYGDYAYFDV
RASENIYSDLA
AATNLAD
QHFWGTPWT




1429
1430
1431
1432
1433
1434





44
CD8B344
NYWIN
NIYPGSDSSNYNEKFKT
EEADYRYTWFVY
KASQNVGTAVA
SASNRYT
QQYSSYPLT




1463
1464
1465
1466
1467
1468





45
CD8B264
SYWIN
NIYPGSSSTNYNEKFKN
EEYSYKSSWFAY
KASQNVGTAVA
SASNRYN
QQYSTYPYT




1497
1498
1499
1500
1501
1502





46
CD8B318
SYWIS
NIYPGSSSSNYNENFKS
EEYSYFPSWFAY
KASQNVGTAVA
SASNRYT
QQYSTYPFT




1531
1532
1533
1534
1535
1536





47
CD8B333
SFWIN
NIYPGSSSTNYSEKFKN
EEYSYKSSWFAY
KASQNVGTAVA
SASNRYN
QQYSTYPYT




1565
1566
1567
1568
1569
1570





48
CD8B366
DDYIH
RIDPANGNPRYAPKFQD
DDEGYYYFDV
RASKSISKYLA
SGSTLQS
QQHNEYPLT




1599
1600
1601
1602
1603
1604





49
CD8B368
SYWIN
NIYPFSSSTNYNEKFKK
EEFSHYPSWFAY
KASQNVGIAVA
SASNRYT
QQYSTDPYT




1633
1634
1635
1636
1637
1638





50
CD8B370
SYWIN
NIYPGSSSTNYNEKFKN
ELGAYYHYSAMDY
KASQNVGTAVA
SASNRYT
QQYSIYPFT




1667
1668
1669
1670
1671
1672





51
CD8B186
SYWMH
NINPSSGYAVYNQKFKD
RVFYGDSWFAY
RASGNIHNYLA
NAKTLAD
QHFWSTTWT




1701
1702
1703
1704
1705
1706





52
CD8B190
SYYMH
YIDPFNGNTNYKQKFKG
PNSNYVGTWFAY
HASQNINVWLS
KASNLHT
QQGQSFPFT




1735
1736
1737
1738
1739
1740





53
CD8B192
DYYMN
VINPYNGGTTYNQRFTG
NYGAMDS
RASGNIHNYLA
NAKTLAD
QHFWITPPT




1769
1770
1771
1772
1773
1774





54
CD8B193
DYYMN
DINPNGGGTSDNPKFKG
TSGTDWYFDV
KASQNVGTAVA
SASNRYT
QQYSSYPFT




1803
1804
1805
1806
1807
1808





55
CD8B214
TAGIQ
WINTHAGESKYADDFKG
SGDYDGSHPFAY
RASQDIRPYLN
YTSRLHS
QQDNTLPYT




1837
1838
1839
1840
1841
1842





56
CD8B230
DYYMN
DINPNGGGTSDNPKFKG
TSGTDWYFDV
KASQNVGTAVA
STSNRYT
QQYSIYPFT




1871
1872
1873
1874
1875
1876





57
CD8B245
DYYMS
LSRNKGNGYTTEYSASVKG
TVTGTLFYYALDY
RASENIYSYLA
NAKTLAA
QHHYGTPLT




1905
1906
1907
1908
1909
1910





58
CD8B248
TYTMH
YINPSSGYTKYNQKFTD
LWAY
RSSQSLVHSSGNTYLH
KGSNRFS
SQSTHVPFT




1939
1940
1941
1942
1943
1944





59
CD8B250
NYVVH
VIWTDGSTDYNAAFIS
NNGYFPAFFAY
KASQNVDTDIT
SASYRYS
QQYNSYPLT




1973
1974
1975
1976
1977
1978





60
CD8B254
SYWIT
DIYPGSGSTNYNEKFKS
ESITTRITPFDH
RSSQSLVHSSGNTYLH
KGSNRFS
SQSTHVPFT




2007
2008
2009
2010
2011
2012





61
CD8B261
SYWIN
NIYPGSSSTNYNEKFKS
ELGGYYRYNAMDY
KASQDINRYLS
RANTLVD
LQYDEFPYT




2041
2042
2043
2044
2045
2046





62
CD8B311
SYWMH
MIHPNSGSTNYNEKFKS
CGYDGAWFAY
SASQGISNCLN
YTSSLHS
QQYSKVPYT




2075
2076
2077
2078
2079
2080





63
CD8B340
NYWMQ
EIDPSDTFTNYNQNFKD
GDWDRDWYFDV
KSSQSLLYSDGKTYLN
LVSKLDS
LQATHFPHT




2109
2110
2111
2112
2113
2114





64
CD8B362
DTYMH
RIDPANGHTKFDPKFQG
RFAY
RASHEISGYLS
AASTLDS
LQYSSYPYT




2143
2144
2145
2146
2147
2148
















TABLE 4







Chothia CDR Amino Acid Sequences of CD8 Antibodies
















HC
HC

LC
LC
LC



Protein
Chothia
Chothia
HC Chothia
Chothia
Chothia
Chothia


#
Name
CDR1
CDR2
CDR3
CDR1
CDR2
CDR3

















1
CD8B191
GYTFTDY
IPSNGG
EDYNNQGFFLDAMD
SQSISDF
YAS
GHSFPY




   7
   8
   9
  10
  11
  12





2
CD8B226
GYTFTDY
IPSNGA
EDYSNQGFFLDAMD
SQSISHY
YAS
GHSFPY




  41
  42
  43
  44
  45
  46





3
CD8B259
GYTFTDY
IPSNGG
EDYGNQGFFLDAMD
SQSISHF
YAS
GHSFPY




  75
  76
  77
  78
  79
  80





4
CD8B298
GYTFTDY
IPNNGG
EDFSNQGFFLDAMD
SQTISDY
YAS
GHSFPY




 109
 110
 111
 112
 113
 114





5
CD8B342
GYTFTDY
IPNNGN
EDYSNQGFFLDAMD
SQTISNY
YAS
GHSFPY




 143
 144
 145
 146
 147
 148





6
CD8B364
GYTFTSY
NPSNGD
SMYYDGRAGA
STDIDDD
EGN
SDNMPL




 177
 178
 179
 180
 181
 182





7
CD8B200
GYTFTNY
DPSDSE
GLTGTGY
SQDISPY
YTS
DNTLPY




 211
 212
 213
 214
 215
 216





8
CD8B247
GYTFTDY
IPNNGG
EDYSNQGFFLDAMD
SQTISHF
YAS
GHSFPY




 245
 246
 247
 248
 249
 250





9
CD8B265
GYSFTDY
IPRNGA
EDFSNQGFFLDAMD
SQSISHY
YAS
GHSFPY




 279
 280
 281
 282
 283
 284





10
CD8B270
GYTFTNY
DPSDSE
GLTGTGY
SQDIRPY
FTS
DNTLPY




 313
 314
 315
 316
 317
 318





11
CD8B213
GYIFTDY
YPNNGI
SIYYDHGGGFP
SQNVDKY
SAS
YNTYP




 347
 348
 349
 350
 351
 352





12
CD8B240
GYTFTDY
IPSNGG
EDYNNQGFFLDAMD
SQSISDF
YAS
GHSFPY




 381
 382
 383
 384
 385
 386





13
CD8B361
GYTFTDY
YPNNGD
SIYYDHGGGFP
SQNVGTY
SAS
YNSYP




 415
 416
 417
 418
 419
 420





14
CD8B246
GFSLSTSGM
WWDDD
RGNYGNYEFA
SQDIRNY
HTS
GNTLPW




 449
 450
 451
 452
 453
 454





15
CD8B268
GYTFTVY
YPGSGN
HEDNHYYDGNSWFA
SGNIHNY
NAK
FWNTPY




 483
 484
 485
 486
 487
 488





16
CD8B271
GFSLSIY
WGGGD
NPHYYGGTYEYFD
SQGISNY
DTS
YSNLPY




 517
 518
 519
 520
 521
 522





17
CD8B273
GYTFTEY
YPGTGS
HEDNHYYDGNSWFA
SGNIHNY
NAK
FWSTPY




 551
 552
 553
 554
 555
 556





18
CD8B288
GYTFTEY
YPGNGN
YEDNHYYDGASWFA
SGNIHNY
NAK
FWSTPF




 585
 586
 587
 588
 589
 590





19
CD8B292
GFNFKDD
DPENGA
HDYGYAMD
SSSVSSSY
STS
YHRSPL




 619
 620
 621
 622
 623
 624





20
CD8B303
GFSLSIY
WGGGS
NPHHYGGSTGAMD
SQDIKKY
YTS
YDNLF




 653
 654
 655
 656
 657
 658





21
CD8B304
GFSLSTSGM
WWDDD
RGNYGNYEFA
SQDIRNY
HTS
GNTLPW




 687
 688
 689
 690
 691
 692





22
CD8B312
GYTFTSF
DPSDSQ
STYYRYDGPFT
SQSINNN
YTS
SNSWPL




 721
 722
 723
 724
 725
 726





23
CD8B347
GYTFTSY
NPSNSY
SGLYNTNHLAWFA
SGNIHNY
NAE
FWNNPL




 755
 756
 757
 758
 759
 760





24
CD8B350
GYTFAAY
NPSNGY
SGLYYTNHLAWCP
SGNIHNY
NAE
FWNSPL




 789
 790
 791
 792
 793
 794





25
CD8B356
GYSITSGY
SYDGS
NHGDAMD
SQNVGTA
SAS
YSSYL




 823
 824
 825
 826
 827
 828





26
CD8B369
GFTFTNT
YTGTGG
TNWDWYFD
SENIYSY
YAK
HYGRPY




 857
 858
 859
 860
 861
 862





27
CD8B371
GFTFSDY
NYDGSI
EDYSNYGFA
SQNINVW
KAS
GQSYPL




 891
 892
 893
 894
 895
 896





28
CD8B182
GYTFTSY
NPTNYY
SGLYNTNHLAWFA
SENIHNY
NAK
FWTTPL




 925
 926
 927
 928
 929
 930





29
CD8B205
GYSFNSY
DPSDSE
VYYSYYSYDATYFD
SENIYSY
NAK
HYTTPL




 959
 960
 961
 962
 963
 964





30
CD8B223
GFSLTSY
WAGGS
HSYYSFDAFD
SQNVNTD
SAS
CNSYPL




 993
 994
 995
 996
 997
 998





31
CD8B234
GYSITSGY
NYDGR
DQGYSKFYFD
SEDIYNR
GAT
YWSFPR




1027
1028
1029
1030
1031
1032





32
CD8B251
GFSLTTY
WSGGS
HSYYHYNAMD
SQNVGTA
SAS
YSSYPF




1061
1062
1063
1064
1065
1066





33
CD8B269
GYSITSGY
SYDGS
NHGDAMD
SQNVGTD
SAS
YKSYPL




1095
1096
1097
1098
1099
1100





34
CD8B290
GFSLSRY
WGGGS
IYFDNYVGFA
SQDVGTV
WTS
YSSYPY




1129
1130
1131
1132
1133
1134





35
CD8B310
GFSLTNY
WTDGS
NNGYFPAFFA
SQTIVHSNGNTY
KVS
GSHAPF




1163
1164
1165
1166
1167
1168





36
CD8B352
GYSITSGY
NYDGR
DQGYSKFYFD
SEDIYNR
GAT
YWSFPR




1197
1198
1199
1200
1201
1202





37
CD8B319
GYSFTAY
NPSAGG
WTNPFD
SQNVGTA
SAS
YNNYL




1231
1232
1233
1234
1235
1236





38
CD8B194
GYTFTSY
YPGSSS
ELGPYYRYSAMV
SQNVGTA
SAS
YSSYPF




1265
1266
1267
1268
1269
1270





39
CD8B231
GYTFTNY
DPSDSE
GLTGTGH
SQDINIY
HTS
DNTLPY




1299
1300
1301
1302
1303
1304





40
CD8B238
GYTFTDY
YTYSGG
DSSDYEFA
SQDIKSY
RAN
YDEFR




1333
1334
1335
1336
1337
1338





41
CD8B255
GFSLNTSGM
FWDDD
RDGYGDYAYFD
SENIYSD
AAT
FWGTPW




1367
1368
1369
1370
1371
1372





42
CD8B324
GYTSTSH
YPGSSS
HS PGHRDYAMD
SQNVGTA
SAS
YSTYPL




1401
1402
1403
1404
1405
1406





43
CD8B337
GFSLSTSGM
FWDDD
RVGYGDYAYFD
SENIYSD
AAT
FWGTPW




1435
1436
1437
1438
1439
1440





44
CD8B344
GYSFTNY
YPGSDS
EEADYRYTWFV
SQNVGTA
SAS
YSSYPL




1469
1470
1471
1472
1473
1474





45
CD8B264
GYSFTSY
YPGSSS
EEYSYKSSWFA
SQNVGTA
SAS
YSTYPY




1503
1504
1505
1506
1507
1508





46
CD8B318
GYTFTSY
YPGSSS
EEYSYFPSWFA
SQNVGTA
SAS
YSTYPF




1537
1538
1539
1540
1541
1542





47
CD8B333
GYSFASF
YPGSSS
EEYSYKSSWFA
SQNVGTA
SAS
YSTYPY




1571
1572
1573
1574
1575
1576





48
CD8B366
GFNIKDD
DPANGN
DDEGYYYFD
SKSISKY
SGS
HNEYPL




1605
1606
1607
1608
1609
1610





49
CD8B368
GYTFTSY
YPFSSS
EEFSHYPSWFA
SQNVGIA
SAS
YSTDPY




1639
1640
1641
1642
1643
1644





50
CD8B370
GYTFTSY
YPGSSS
ELGAYYHYSAMD
SQNVGTA
SAS
YSIYPF




1673
1674
1675
1676
1677
1678





51
CD8B186
GYIFTSY
NPSSGY
RVFYGDSWFA
SGNIHNY
NAK
FWSTTW




1707
1708
1709
1710
1711
1712





52
CD8B190
GYSFTSY
DPFNGN
PNSNYVGTWFA
SQNINVW
KAS
GQSFPF




1741
1742
1743
1744
1745
1746





53
CD8B192
GYTFTDY
NPYNGG
NYGAMD
SGNIHNY
NAK
FWITPP




1775
1776
1777
1778
1779
1780





54
CD8B193
GYKFTDY
NPNGGG
TSGTDWYFD
SQNVGTA
SAS
YSSYPF




1809
1810
1811
1812
1813
1814





55
CD8B214
GYTFTTA
NTHAGE
SGDYDGSHPFA
SQDIRPY
YTS
DNTLPY




1843
1844
1845
1846
1847
1848





56
CD8B230
GYTFTDY
NPNGGG
TSGTDWYFD
SQNVGTA
STS
YSIYPF




1877
1878
1879
1880
1881
1882





57
CD8B245
GFTFTDY
RNKGNGYT
TVTGTLFYYALD
SENIYSY
NAK
HYGTPL




1911
1912
1913
1914
1915
1916





58
CD8B248
GYTFTTY
NPSSGY
LWA
SQSLVHSSGNTY
KGS
STHVPF




1945
1946
1947
1948
1949
1950





59
CD8B250
GFSLSNY
WTDGS
NNGYFPAFFA
SQNVDTD
SAS
YNSYPL




1979
1980
1981
1982
1983
1984





60
CD8B254
GYTFSSY
YPGSGS
ESITTRITPFD
SQSLVHSSGNTY
KGS
STHVPF




2013
2014
2015
2016
2017
2018





61
CD8B261
GYTFNSY
YPGSSS
ELGGYYRYNAMD
SQDINRY
RAN
YDEFPY




2047
2048
2049
2050
2051
2052





62
CD8B311
GYTFTSY
HPNSGS
CGYDGAWFA
SQGISNC
YTS
YSKVPY




2081
2082
2083
2084
2085
2086





63
CD8B340
GYTFTNY
DPSDTF
GDWDRDWYFD
SQSLLYSDGKTY
LVS
ATHFPH




2115
2116
2117
2118
2119
2120





64
CD8B362
GFNIKDT
DPANGH
RFA
SHEISGY
AAS
YSSYPY




2149
2150
2151
2152
2153
2154
















TABLE 5







AbM CDR Amino Acid Sequences of CD8 Antibodies















Protein
HC AbM
HC AbM
HC AbM
LC AbM
LC AbM
LC AbM


#
Name
CDR1
CDR2
CDR3
CDR1
CDR2
CDR3

















1
CD8B191
GYTFTDYYMN
RVIPSNGGTI
EDYNNQGFFLDAMDY
RASQSISDFLH
YASQSIS
QNGHSFPYT




  13
  14
  15
  16
  17
  18





2
CD8B226
GYTFTDYYMN
RIIPSNGATI
EDYSNQGFFLDAMDY
RASQSISHYLH
YASQSIS
QNGHSFPYT




  47
  48
  49
  50
  51
  52





3
CD8B259
GYTFTDYYMN
RVIPSNGGTI
EDYGNQGFFLDAMDY
RASQSISHFLH
YASQSIS
QSGHSFPYT




  81
  82
  83
  84
  85
  86





4
CD8B298
GYTFTDYYMN
RVIPNNGGTR
EDFSNQGFFLDAMDY
RASQTISDYLH
YASQSIS
QNGHSFPYT




 115
 116
 117
 118
 119
 120





5
CD8B342
GYTFTDYYVN
RVIPNNGNVI
EDYSNQGFFLDAMDY
RASQTISNYLH
YASQSIS
QNGHSFPYT




 149
 150
 151
 152
 153
 154





6
CD8B364
GYTFTSYWMH
EINPSNGDSY
SMYYDGRAGAY
ITSTDIDDDMN
EGNTLRP
LQSDNMPLT




 183
 184
 185
 186
 187
 188





7
CD8B200
GYTFTNYWIH
NIDPSDSETH
GLTGTGYY
RASQDISPYLN
YTSKLHS
QQDNTLPYT




 217
 218
 219
 220
 221
 222





8
CD8B247
GYTFTDYYMN
RVIPNNGGTI
EDYSNQGFFLDAMDY
RASQTISHFLH
YASQSIS
QSGHSFPYT




 251
 252
 253
 254
 255
 256





9
CD8B265
GYSFTDYYMN
RVIPRNGATT
EDFSNQGFFLDAMDY
RASQSISHYLH
YASQSIS
QNGHSFPYT




 285
 286
 287
 288
 289
 290





10
CD8B270
GYTFTNYWMH
NIDPSDSETH
GLTGTGYY
RASQDIRPYLN
FTSKLHS
QQDNTLPYT




 319
 320
 321
 322
 323
 324





11
CD8B213
GYIFTDYYMD
YIYPNNGITS
SIYYDHGGGFPY
KASQNVDKYVA
SASYRYS
QQYNTYPS




 353
 354
 355
 356
 357
 358





12
CD8B240
GYTFTDYYMN
RVIPSNGGTI
EDYNNQGFFLDAMDY
RASQSISDFLH
YASQSIS
QNGHSFPYT




 387
 388
 389
 390
 391
 392





13
CD8B361
GYTFTDYYMD
YIYPNNGDTR
SIYYDHGGGFPY
KASQNVGTYVA
SASYRYS
QQYNSYPT




 421
 422
 423
 424
 425
 426





14
CD8B246
GFSLSTSGMNVG
HIWWDDDKY
RGNYGNYEFAY
RASQDIRNYLN
HTSRLHS
QQGNTLPWT




 455
 456
 457
 458
 459
 460





15
CD8B268
GYTFTVYTIH
WFYPGSGNIK
HEDNHYYDGNSWFAY
RASGNIHNYLA
NAKTLAD
QHFWNTPYT




 489
 490
 491
 492
 493
 494





16
CD8B271
GFSLSIYSIH
MIWGGGDTD
NPHYYGGTYEYFDV
SASQGISNYLN
DTSILYS
QQYSNLPYT




 523
 524
 525
 526
 527
 528





17
CD8B273
GYTFTEYTIH
WFYPGTGSIK
HEDNHYYDGNSWFAY
RASGNIHNYLA
NAKTLAD
QHFWSTPYT




 557
 558
 559
 560
 561
 562





18
CD8B288
GYTFTEYTIH
WFYPGNGNMR
YEDNHYYDGASWFAY
RASGNIHNYLA
NAKTLAD
QHFWSTPFT




 591
 592
 593
 594
 595
 596





19
CD8B292
GFNFKDDYIY
WIDPENGATE
HDYGYAMDY
TASSSVSSSYLH
STSNLAS
HQYHRSPLT




 625
 626
 627
 628
 629
 630





20
CD8B303
GFSLSTYSTH
MIWGGGSTD
NPHHYGGSTGAMDY
KASQDIKKYMA
YTSSLQP
LQYDNLFT




 659
 660
 661
 662
 663
 664





21
CD8B304
GFSLSTSGMNVG
HIWWDDDKY
RGNYGNYEFAY
RASQDIRNYLN
HTSRLHS
QQGNTLPWT




 693
 694
 695
 696
 697
 698





22
CD8B312
GYTFTSFWMH
NVDPSDSQTH
STYYRYDGPFTY
RASQSINNNLH
YTSQSIS
QQSNSWPLT




 727
 728
 729
 730
 731
 732





23
CD8B347
GYTFTSYWMN
AVNPSNSYTE
SGLYNTNHLAWFAY
RASGNIHNYLA
NAETLAD
QHFWNNPLT




 761
 762
 763
 764
 765
 766





24
CD8B350
GYTFAAYWIN
SINPSNGYTE
SGLYYTNHLAWCPY
RASGNIHNYLA
NAETLAD
QHFWNSPLT




 795
 796
 797
 798
 799
 800





25
CD8B356
GYSITSGYYWNYI
SYDGSNN
NHGDAMDY
KASQNVGTAVA
SASYRYT
QQYSSYLT




 829
 830
 831
 832
 833
 834





26
CD8B369
GFTFTNTYIS
WIYTGTGGTW
TNWDWYFDV
RASENIYSYLA
YAKTLTD
QHHYGRPYT




 863
 864
 865
 866
 867
 868





27
CD8B371
GFTFSDYYMA
HINYDGSITY
EDYSNYGFAY
HASQNINVWLS
KASNLHT
QQGQSYPLT




 897
 898
 899
 900
 901
 902





28
CD8B182
GYTFTSYWMN
AVNPTNYYTE
SGLYNTNHLAWFAY
RASENIHNYLA
NAKTLAN
QHFWTTPLT




 931
 932
 933
 934
 935
 936





29
CD8B205
GYSFNSYWMH
NIDPSDSETH
VYYSYYSYDATYFDY
RASENIYSYLA
NAKTLAE
QHHYTTPLT




 965
 966
 967
 968
 969
 970





30
CD8B223
GFSLTSYSVH
VIWAGGSTN
HSYYSFDAFDY
KASQNVNTDVA
SASYRYS
QQCNSYPLT




 999
1000
1001
1002
1003
1004





31
CD8B234
GYSITSGYYWN
YINYDGRNN
DQGYSKFYFDY
KASEDIYNRLA
GATSLET
QQYWSFPRT




1033
1034
1035
1036
1037
1038





32
CD8B251
GFSLTTYAVH
VIWSGGSTD
HSYYHYNAMDN
KASQNVGTAVA
SASNRYT
QQYSSYPFT




1067
1068
1069
1070
1071
1072





33
CD8B269
GYSITSGYYWN
YISYDGSNN
NHGDAMDH
KASQNVGTDVA
SASYRYS
QQYKSYPLT




1101
1102
1103
1104
1105
1106





34
CD8B290
GFSLSRYSVH
MIWGGGSTD
IYFDNYVGFAY
KASQDVGTVVA
WTSTRHT
QQYSSYPYT




1135
1136
1137
1138
1139
1140





35
CD8B310
GFSLTNYAVH
VIWTDGSTD
NNGYFPAFFAY
RSSQTIVHSNGNTYLE
KVSNRFS
FQGSHAPFT




1169
1170
1171
1172
1173
1174





36
CD8B352
GYSITSGYYWN
YINYDGRNN
DQGYSKFYFDY
KASEDIYNRLA
GATSLET
QQYWSFPRT




1203
1204
1205
1206
1207
1208





37
CD8B319
GYSFTAYYMH
EINPSAGGTT
WTNPFDY
KASQNVGTAVA
SASYRYT
QQYNNYLT




1237
1238
1239
1240
1241
1242





38
CD8B194
GYTFTSYWIN
NIYPGSSSTN
ELGPYYRYSAMVY
KASQNVGTAVA
SASNRYT
QQYSSYPFT




1271
1272
1273
1274
1275
1276





39
CD8B231
GYTFTNYWMH
NIDPSDSETH
GLTGTGHY
RASQDINIYLN
HTSRLHS
QQDNTLPYT




1305
1306
1307
1308
1309
1310





40
CD8B238
GYTFTDYSMD
YIYTYSGGAG
DSSDYEFAY
KASQDIKSYLS
RANRLVD
LQYDEFRT




1339
1340
1341
1342
1343
1344





41
CD8B255
GFSLNTSGMGVS
HIFWDDDKR
RDGYGDYAYFDV
RASENIYSDLA
AATILTD
QHFWGTPWT




1373
1374
1375
1376
1377
1378





42
CD8B324
GYTSTSHWIH
NIYPGSSSTN
HSPGHRDYAMDY
KASQNVGTAVA
SASNRYT
QQYSTYPLT




1407
1408
1409
1410
1411
1412





43
CD8B337
GFSLSTSGMGVS
HIFWDDDRR
RVGYGDYAYFDV
RASENIYSDLA
AATNLAD
QHFWGTPWT




1441
1442
1443
1444
1445
1446





44
CD8B344
GYSFTNYWIN
NIYPGSDSSN
EEADYRYTWFVY
KASQNVGTAVA
SASNRYT
QQYSSYPLT




1475
1476
1477
1478
1479
1480





45
CD8B264
GYSFTSYWIN
NIYPGSSSTN
EEYSYKSSWFAY
KASQNVGTAVA
SASNRYN
QQYSTYPYT




1509
1510
1511
1512
1513
1514





46
CD8B318
GYTFTSYWIS
NIYPGSSSSN
EEYSYFPSWFAY
KASQNVGTAVA
SASNRYT
QQYSTYPFT




1543
1544
1545
1546
1547
1548





47
CD8B333
GYSFASFWIN
NIYPGSSSTN
EEYSYKSSWFAY
KASQNVGTAVA
SASNRYN
QQYSTYPYT




1577
1578
1579
1580
1581
1582





48
CD8B366
GFNIKDDYIH
RIDPANGNPR
DDEGYYYFDV
RASKSISKYLA
SGSTLQS
QQHNEYPLT




1611
1612
1613
1614
1615
1616





49
CD8B368
GYTFTSYWIN
NIYPFSSSTN
EEFSHYPSWFAY
KASQNVGIAVA
SASNRYT
QQYSTDPYT




1645
1646
1647
1648
1649
1650





50
CD8B370
GYTFTSYWIN
NIYPGSSSTN
ELGAYYHYSAMDY
KASQNVGTAVA
SASNRYT
QQYSIYPFT




1679
1680
1681
1682
1683
1684





51
CD8B186
GYIFTSYWMH
NINPSSGYAV
RVFYGDSWFAY
RASGNIHNYLA
NAKTLAD
QHFWSTTWT




1713
1714
1715
1716
1717
1718





52
CD8B190
GYSFTSYYMH
YIDPFNGNTN
PNSNYVGTWFAY
HASQNINVWLS
KASNLHT
QQGQSFPFT




1747
1748
1749
1750
1751
1752





53
CD8B192
GYTFTDYYMN
VINPYNGGTT
NYGAMDS
RASGNIHNYLA
NAKTLAD
QHFWITPPT




1781
1782
1783
1784
1785
1786





54
CD8B193
GYKFTDYYMN
DINPNGGGTS
TSGTDWYFDV
KASQNVGTAVA
SASNRYT
QQYSSYPFT




1815
1816
1817
1818
1819
1820





55
CD8B214
GYTFTTAGIQ
WINTHAGESK
SGDYDGSHPFAY
RASQDIRPYLN
YTSRLHS
QQDNTLPYT




1849
1850
1851
1852
1853
1854





56
CD8B230
GYTFTDYYMN
DINPNGGGTS
TSGTDWYFDV
KASQNVGTAVA
STSNRYT
QQYSIYPFT




1883
1884
1885
1886
1887
1888





57
CD8B245
GFTFTDYYMS
LSRNKGNGYTTE
TVTGTLFYYALDY
RASENIYSYLA
NAKTLAA
QHHYGTPLT




1917
1918
1919
1920
1921
1922





58
CD8B248
GYTFTTYTMH
YINPSSGYTK
LWAY
RSSQSLVHSSGNTYLH
KGSNRFS
SQSTHVPFT




1951
1952
1953
1954
1955
1956





59
CD8B250
GFSLSNYVVH
VIWTDGSTD
NNGYFPAFFAY
KASQNVDTDIT
SASYRYS
QQYNSYPLT




1985
1986
1987
1988
1989
1990





60
CD8B254
GYTFSSYWIT
DIYPGSGSTN
ESITTRITPFDH
RSSQSLVHSSGNTYLH
KGSNRFS
SQSTHVPFT




2019
2020
2021
2022
2023
2024





61
CD8B261
GYTFNSYWIN
NIYPGSSSTN
ELGGYYRYNAMDY
KASQDINRYLS
RANTLVD
LQYDEFPYT




2053
2054
2055
2056
2057
2058





62
CD8B311
GYTFTSYWMH
MIHPNSGSTN
CGYDGAWFAY
SASQGISNCLN
YTSSLHS
QQYSKVPYT




2087
2088
2089
2090
2091
2092





63
CD8B340
GYTFTNYWMQ
EIDPSDTFTN
GDWDRDWYFDV
KSSQSLLYSDGKTYLN
LVSKLDS
LQATHFPHT




2121
2122
2123
2124
2125
2126





64
CD8B362
GFNIKDTYMH
RIDPANGHTK
RFAY
RASHEISGYLS
AASTLDS
LQYSSYPYT




2155
2156
2157
2158
2159
2160
















TABLE 6







Contact CDR Amino Acid Sequences of CD8 Antibodies
















HC
HC
HC
LC
LC
LC



Protein
Contact
Contact
Contact
Contact
Contact
Contact


#
Name
CDR1
CDR2
CDR3
CDR1 
CDR2
CDR3

















1
CD8B191
TDYYMN
WIGRVIPSNGGTI
AREDYNNQGFFLDAMD
SDFLHWY
LLIKYASQSI
QNGHSFPY




  19
  20
  21
  22
  23
  24





2
CD8B226
TDYYMN
WIGRIIPSNGATI
AREDYSNQGFFLDAMD
SHYLHWY
LLIKYASQSI
QNGHSFPY




  53
  54
  55
  56
  57
  58





3
CD8B259
TDYYMN
WIGRVIPSNGGTI
AREDYGNQGFFLDAMD
SHFLHWY
LLIKYASQSI
QSGHSFPY




  87
  88
  89
  90
  91
  92





4
CD8B298
TDYYMN
WIGRVIPNNGGTR
AREDFSNQGFFLDAMD
SDYLHWY
LLIKYASQSI
QNGHSFPY




 121
 122
 123
 124
 125
 126





5
CD8B342
TDYYVN
WIGRVIPNNGNVI
TREDYSNQGFFLDAMD
SNYLHWY
LLIKYASQSI
QNGHSFPY




 155
 156
 157
 158
 159
 160





6
CD8B364
TSYWMH
WIGEINPSNGDSY
TRSMYYDGRAGA
DDDMNWY
LLISEGNTLR
LQSDNMPL




 189
 190
 191
 192
 193
 194





7
CD8B200
TNYWIH
WIGNIDPSDSETH
ASGLTGTGY
SPYLNWY
LLIYYTSKLH
QQDNTLPY




 223
 224
 225
 226
 227
 228





8
CD8B247
TDYYMN
WIGRVIPNNGGTI
AREDYSNQGFFLDAMD
SHFLHWY
LLIKYASQSI
QSGHSFPY




 257
 258
 259
 260
 261
 262





9
CD8B265
TDYYMN
WIGRVIPRNGATT
AREDFSNQGFFLDAMD
SHYLHWY
LLIKYASQSI
QNGHSFPY




 291
 292
 293
 294
 295
 296





10
CD8B270
TNYWMH
WIGNIDPSDSETH
ASGLTGTGY
RPYLNWY
LLIYFTSKLH
QQDNTLPY




 325
 326
 327
 328
 329
 330





11
CD8B213
TDYYMD
WIGYIYPNNGITS
ARSIYYDHGGGFP
DKYVAWY
ALIYSASYRY
QQYNTYP




 359
 360
 361
 362
 363
 364





12
CD8B240
TDYYMN
WIGRVIPSNGGTI
AREDYNNQGFFLDAMD
SDFLHWY
LLIKYASQSI
QNGHSFPY




 393
 394
 395
 396
 397
 398





13
CD8B361
TDYYMD
WIGYIYPNNGDTR
ARSIYYDHGGGFP
GTYVAWY
ALIYSASYRY
QQYNSYP




 427
 428
 429
 430
 431
 432





14
CD8B246
STSGMNVG
WLAHIWWDDDKY
ARRGNYGNYEFA
RNYLNWY
LLIYHTSRLH
QQGNTLPW




 461
 462
 463
 464
 465
 466





15
CD8B268
TVYTIH
WIGWFYPGSGNIK
ARHEDNHYYDGNSWFA
HNYLAWF
LLVYNAKTLA
QHFWNTPY




 495
 496
 497
 498
 499
 500





16
CD8B271
SIYSIH
WLGMIWGGGDTD
ARNPHYYGGTYEYFD
SNYLNWY
LLIYDTSILY
QQYSNLPY




 529
 530
 531
 532
 533
 534





17
CD8B273
TEYTIH
WIGWFYPGTGSIK
ARHEDNHYYDGNSWFA
HNYLAWF
LLVYNAKTLA
QHFWSTPY




 563
 564
 565
 566
 567
 568





18
CD8B288
TEYTIH
WIGWFYPGNGNMR
ARYEDNHYYDGASWFA
HNYLAWF
LLVYNAKTLA
QHFWSTPF




 597
 598
 599
 600
 601
 602





19
CD8B292
KDDYIY
WIGWIDPENGATE
SLHDYGYAMD
SSSYLHWY
LWIYSTSNLA
HQYHRSPL




 631
 632
 633
 634
 635
 636





20
CD8B303
STYSTH
WLGMIWGGGSTD
ARNPHHYGGSTGAMD
KKYMAWY
LLIHYTSSLQ
LQYDNLF




 665
 666
 667
 668
 669
 670





21
CD8B304
STSGMNVG
WLAHIWWDDDKY
ARRGNYGNYEFA
RNYLNWY
LLIYHTSRLH
QQGNTLPW




 699
 700
 701
 702
 703
 704





22
CD8B312
TSFWMH
WIGNVDPSDSQTH
ARSTYYRYDGPFT
NNNLHWY
LLIKYTSQSI
QQSNSWPL




 733
 734
 735
 736
 737
 738





23
CD8B347
TSYWMN
WIGAVNPSNSYTE
ARSGLYNTNHLAWFA
HNYLAWY
LLVFNAETLA
QHFWNNPL




 767
 768
 769
 770
 771
 772





24
CD8B350
AAYWIN
WIGSINPSNGYTE
SRSGLYYTNHLAWCP
HNYLAWY
VLVYNAETLA
QHFWNSPL




 801
 802
 803
 804
 805
 806





25
CD8B356
TSGYYWN
WMGYISYDGSNN
VRNHGDAMD
GTAVAWY
LLIYSASYRY
QQYSSYL




 835
 836
 837
 838
 839
 840





26
CD8B369
TNTYIS
WIAWIYTGTGGTW
ARTNWDWYFD
YSYLAWY
LLVYYAKTLT
QHHYGRPY




 869
 870
 871
 872
 873
 874





27
CD8B371
SDYYMA
WVAHINYDGSITY
AREDYSNYGFA
NVWLSWY
LLIYKASNLH
QQGQSYPL




 903
 904
 905
 906
 907
 908





28
CD8B182
TSYWMN
WIGAVNPTNYYTE
ARSGLYNTNHLAWFA
HNYLAWY
LLVYNAKTLA
QHFWTTPL




 937
 938
 939
 940
 941
 942





29
CD8B205
NSYWMH
WIGNIDPSDSETH
ARVYYSYYSYDATYFD
YSYLAWY
LLVYNAKTLA
QHHYTTPL




 971
 972
 973
 974
 975
 976





30
CD8B223
TSYSVH
WLGVIWAGGSTN
AKHSYYSFDAFD
NTDVAWY
ALIYSASYRY
QQCNSYPL




1005
1006
1007
1008
1009
1010





31
CD8B234
TSGYYWN
WMGYINYDGRNN
SRDQGYSKFYFD
YNRLAWY
LLISGATSLE
QQYWSFPR




1039
1040
1041
1042
1043
1044





32
CD8B251
TTYAVH
WLGVIWSGGSTD
ARHSYYHYNAMD
GTAVAWY
LLIYSASNRY
QQYSSYPF




1073
1074
1075
1076
1077
1078





33
CD8B269
TSGYYWN
WMGYISYDGSNN
VRNHGDAMD
GTDVAWY
ALIYSASYRY
QQYKSYPL




1107
1108
1109
1110
1111
1112





34
CD8B290
SRYSVH
WLGMIWGGGSTD
ARIYFDNYVGFA
GTVVAWY
LLIFWTSTRH
QQYSSYPY




1141
1142
1143
1144
1145
1146





35
CD8B310
TNYAVH
WLGVIWTDGSTD
ARNNGYFPAFFA
VHSNGNTYLEWY
LLMYKVSNRF
FQGSHAPF




1175
1176
1177
1178
1179
1180





36
CD8B352
TSGYYWN
WMGYINYDGRNN
ARDQGYSKFYFD
YNRLAWY
LLISGATSLE
QQYWSFPR




1209
1210
1211
1212
1213
1214





37
CD8B319
TAYYMH
WIGEINPSAGGTT
ARWTNPFD
GTAVAWY
LLIYSASYRY
QQYNNYL




1243
1244
1245
1246
1247
1248





38
CD8B194
TSYWIN
WIGNIYPGSSSTN
ARELGPYYRYSAMV
GTAVAWY
LLIYSASNRY
QQYSSYPF




1277
1278
1279
1280
1281
1282





39
CD8B231
TNYWMH
WIGNIDPSDSETH
ASGLTGTGH
NIYLNWY
CLIYHTSRLH
QQDNTLPY




1311
1312
1313
1314
1315
1316





40
CD8B238
TDYSMD
WIGYIYTYSGGAG
ARDSSDYEFA
KSYLSWF
TLIYRANRLV
LQYDEFR




1345
1346
1347
1348
1349
1350





41
CD8B255
NTSGMGVS
WLAHIFWDDDKR
ARRDGYGDYAYFD
YSDLAWY
LLVYAATILT
QHFWGTPW




1379
1380
1381
1382
1383
1384





42
CD8B324
TSHWIH
WIGNIYPGSSSTN
ARHSPGHRDYAMD
GTAVAWY
LLIASASNRY
QQYSTYPL




1413
1414
1415
1416
1417
1418





43
CD8B337
STSGMGVS
WLAHIFWDDDRR
ARRVGYGDYAYFD
YSDLAWY
LLVYAATNLA
QHFWGTPW




1447
1448
1449
1450
1451
1452





44
CD8B344
TNYWIN
WIGNIYPGSDSSN
AREEADYRYTWFV
GTAVAWY
LLIYSASNRY
QQYSSYPL




1481
1482
1483
1484
1485
1486





45
CD8B264
TSYWIN
WIGNIYPGSSSTN
AREEYSYKSSWFA
GTAVAWY
LLIYSASNRY
QQYSTYPY




1515
1516
1517
1518
1519
1520





46
CD8B318
TSYWIS
WIGNIYPGSSSSN
AREEYSYFPSWFA
GTAVAWF
LLIYSASNRY
QQYSTYPF




1549
1550
1551
1552
1553
1554





47
CD8B333
ASFWIN
WIGNIYPGSSSTN
AREEYSYKSSWFA
GTAVAWY
LLIYSASNRY
QQYSTYPY




1583
1584
1585
1586
1587
1588





48
CD8B366
KDDYIH
WIGRIDPANGNPR
ARDDEGYYYFD
SKYLAWY
VLIYSGSTLQ
QQHNEYPL




1617
1618
1619
1620
1621
1622





49
CD8B368
TSYWIN
WIGNIYPFSSSTN
AREEFSHYPSWFA
GIAVAWF
LLIYSASNRY
QQYSTDPY




1651
1652
1653
1654
1655
1656





50
CD8B370
TSYWIN
WIGNIYPGSSSTN
TRELGAYYHYSAMD
GTAVAWY
LLIYSASNRY
QQYSIYPF




1685
1686
1687
1688
1689
1690





51
CD8B186
TSYWMH
WIGNINPSSGYAV
ARRVFYGDSWFA
HNYLAWY
LLVYNAKTLA
QHFWSTTW




1719
1720
1721
1722
1723
1724





52
CD8B190
TSYYMH
WIGYIDPFNGNTN
ASPNSNYVGTWFA
NVWLSWY
LLIYKASNLH
QQGQSFPF




1753
1754
1755
1756
1757
1758





53
CD8B192
TDYYMN
WIGVINPYNGGTT
ARNYGAMD
HNYLAWY
LLVSNAKTLA
QHFWITPP




1787
1788
1789
1790
1791
1792





54
CD8B193
TDYYMN
WIGDINPNGGGTS
ARTSGTDWYFD
GTAVAWY
LLIYSASNRY
QQYSSYPF




1821
1822
1823
1824
1825
1826





55
CD8B214
TTAGIQ
WIGWINTHAGESK
ARSGDYDGSHPFA
RPYLNWY
LLIYYTSRLH
QQDNTLPY




1855
1856
1857
1858
1859
1860





56
CD8B230
TDYYMN
WIGDINPNGGGTS
ARTSGTDWYFD
GTAVAWY
LLIYSTSNRY
QQYSIYPF




1889
1890
1891
1892
1893
1894





57
CD8B245
TDYYMS
WLALSRNKGNGYTTE
ARTVTGTLFYYALD
YSYLAWY
FLVYNAKTLA
QHHYGTPL




1923
1924
1925
1926
1927
1928





58
CD8B248
TTYTMH
WIGYINPSSGYTK
ARLWA
VHSSGNTYLHWY
LLIYKGSNRF
SQSTHVPF




1957
1958
1959
1960
1961
1962





59
CD8B250
SNYVVH
WLGVIWTDGSTD
ARNNGYFPAFFA
DTDITWY
ALIYSASYRY
QQYNSYPL




1991
1992
1993
1994
1995
1996





60
CD8B254
SSYWIT
WVGDIYPGSGSTN
ARESITTRITPFD
VHSSGNTYLHWY
LLIYKGSNRF
SQSTHVPF




2025
2026
2027
2028
2029
2030





61
CD8B261
NSYWIN
WIGNIYPGSSSTN
ARELGGYYRYNAMD
NRYLSWF
TLIYRANTLV
LQYDEFPY




2059
2060
2061
2062
2063
2064





62
CD8B311
TSYWMH
WIGMIHPNSGSTN
ARCGYDGAWFA
SNCLNWY
LLIHYTSSLH
QQYSKVPY




2093
2094
2095
2096
2097
2098





63
CD8B340
TNYWMQ
WIGEIDPSDTFTN
ARGDWDRDWYFD
LYSDGKTYLNWL
LLIYLVSKLD
LQATHFPH




2127
2128
2129
2130
2131
2132





64
CD8B362
KDTYMH
WIGRIDPANGHTK
AIRFA
SGYLSWL
RLIYAASTLD
LQYSSYPY




2161
2162
2163
2164
2165
2166
















TABLE 7







IMGT CDR Amino Acid Sequences of CD8 Antibodies















Protein
HC IMGT
HC IMGT
HC IMGT
LC IMGT
LC IMGT
LC IMGT


#
Name
CDR1
CDR2
CDR3
CDR1
CDR2
CDR3 

















1
CD8B191
GYTFTDYY
VIPSNGGT
AREDYNNQGFFLDAMDY
QSISDF
YAS
QNGHSFPYT




  25
  26
  27
  28
  29
  30





2
CD8B226
GYTFTDYY
IIPSNGAT
AREDYSNQGFFLDAMDY
QSISHY
YAS
QNGHSFPYT




  59
  60
  61
  62
  63
  64





3
CD8B259
GYTFTDYY
VIPSNGGT
AREDYGNQGFFLDAMDY
QSISHF
YAS
QSGHSFPYT




  93
  94
  95
  96
  97
  98





4
CD8B298
GYTFTDYY
VIPNNGGT
AREDFSNQGFFLDAMDY
QTISDY
YAS
QNGHSFPYT




 127
 128
 129
 130
 131
 132





5
CD8B342
GYTFTDYY
VIPNNGNV
TREDYSNQGFFLDAMDY
QTISNY
YAS
QNGHSFPYT




 161
 162
 163
 164
 165
 166





6
CD8B364
GYTFTSYW
INPSNGDS
TRSMYYDGRAGAY
TDIDDD
EGN
LQSDNMPLT




 195
 196
 197
 198
 199
 200





7
CD8B200
GYTFTNYW
IDPSDSET
ASGLTGTGYY
QDISPY
YTS
QQDNTLPYT




 229
 230
 231
 232
 233
 234





8
CD8B247
GYTFTDYY
VIPNNGGT
AREDYSNQGFFLDAMDY
QTISHF
YAS
QSGHSFPYT




 263
 264
 265
 266
 267
 268





9
CD8B265
GYSFTDYY
VIPRNGAT
AREDFSNQGFFLDAMDY
QSISHY
YAS
QNGHSFPYT




 297
 298
 299
 300
 301
 302





10
CD8B270
GYTFTNYW
IDPSDSET
ASGLTGTGYY
QDIRPY
FTS
QQDNTLPYT




 331
 332
 333
 334
 335
 336





11
CD8B213
GYIFTDYY
IYPNNGIT
ARSIYYDHGGGFPY
QNVDKY
SAS
QQYNTYPS




 365
 366
 367
 368
 369
 370





12
CD8B240
GYTFTDYY
VIPSNGGT
AREDYNNQGFFLDAMDY
QSISDF
YAS
QNGHSFPYT




 399
 400
 401
 402
 403
 404





13
CD8B361
GYTFTDYY
IYPNNGDT
ARSIYYDHGGGFPY
QNVGTY
SAS
QQYNSYPT




 433
 434
 435
 436
 437
 438





14
CD8B246
GFSLSTSGMN
IWWDDDK
ARRGNYGNYEFAY
QDIRNY
HTS
QQGNTLPWT




 467
 468
 469
 470
 471
 472





15
CD8B268
GYTFTVYT
FYPGSGNI
ARHEDNHYYDGNSWFAY
GNIHNY
NAK
QHFWNTPYT




 501
 502
 503
 504
 505
 506





16
CD8B271
GFSLSIYS
IWGGGDT
ARNPHYYGGTYEYFDV
QGISNY
DTS
QQYSNLPYT




 535
 536
 537
 538
 539
 540





17
CD8B273
GYTFTEYT
FYPGTGSI
ARHEDNHYYDGNSWFAY
GNIHNY
NAK
QHFWSTPYT




 569
 570
 571
 572
 573
 574





18
CD8B288
GYTFTEYT
FYPGNGNM
ARYEDNHYYDGASWFAY
GNIHNY
NAK
QHFWSTPFT




 603
 604
 605
 606
 607
 608





19
CD8B292
GFNFKDDY
IDPENGAT
SLHDYGYAMDY
SSVSSSY
STS
HQYHRSPLT




 637
 638
 639
 640
 641
 642





20
CD8B303
GFSLSIYS
IWGGGST
ARNPHHYGGSTGAMDY
QDIKKY
YTS
LQYDNLFT




 671
 672
 673
 674
 675
 676





21
CD8B304
GFSLSTSGMN
IWWDDDK
ARRGNYGNYEFAY
QDIRNY
HTS
QQGNTLPWT




 705
 706
 707
 708
 709
 710





22
CD8B312
GYTFTSFW
VDPSDSQT
ARSTYYRYDGPFTY
QSINNN
YTS
QQSNSWPLT




 739
 740
 741
 742
 743
 744





23
CD8B347
GYTFTSYW
VNPSNSYT
ARSGLYNTNHLAWFAY
GNIHNY
NAE
QHFWNNPLT




 773
 774
 775
 776
 777
 778





24
CD8B350
GYTFAAYW
INPSNGYT
SRSGLYYTNHLAWCPY
GNIHNY
NAE
QHFWNSPLT




 807
 808
 809
 810
 811
 812





25
CD8B356
GYSITSGYY
ISYDGSN
VRNHGDAMDY
QNVGTA
SAS
QQYSSYLT




 841
 842
 843
 844
 845
 846





26
CD8B369
GFTFTNTY
IYTGTGGT
ARTNWDWYFDV
ENIYSY
YAK
QHHYGRPYT




 875
 876
 877
 878
 879
 880





27
CD8B371
GFTFSDYY
INYDGSIT
AREDYSNYGFAY
QNINVW
KAS
QQGQSYPLT




 909
 910
 911
 912
 913
 914





28
CD8B182
GYTFTSYW
VNPTNYYT
ARSGLYNTNHLAWFAY
ENIHNY
NAK
QHFWTTPLT




 943
 944
 945
 946
 947
 948





29
CD8B205
GYSFNSYW
IDPSDSET
ARVYYSYYSYDATYFDY
ENIYSY
NAK
QHHYTTPLT




 977
 978
 979
 980
 981
 982





30
CD8B223
GFSLTSYS
IWAGGST
AKHSYYSFDAFDY
QNVNTD
SAS
QQCNSYPLT




1011
1012
1013
1014
1015
1016





31
CD8B234
GYSITSGYY
INYDGRN
SRDQGYSKFYFDY
EDIYNR
GAT
QQYWSFPRT




1045
1046
1047
1048
1049
1050





32
CD8B251
GFSLTTYA
IWSGGST
ARHSYYHYNAMDN
QNVGTA
SAS
QQYSSYPFT




1079
1080
1081
1082
1083
1084





33
CD8B269
GYSITSGYY
ISYDGSN
VRNHGDAMDH
QNVGTD
SAS
QQYKSYPLT




1113
1114
1115
1116
1117
1118





34
CD8B290
GFSLSRYS
IWGGGST
ARIYFDNYVGFAY
QDVGTV
WTS
QQYSSYPYT




1147
1148
1149
1150
1151
1152





35
CD8B310
GFSLTNYA
IWTDGST
ARNNGYFPAFFAY
QTIVHSNGNTY
KVS
FQGSHAPFT




1181
1182
1183
1184
1185
1186





36
CD8B352
GYSITSGYY
INYDGRN
ARDQGYSKFYFDY
EDIYNR
GAT
QQYWSFPRT




1215
1216
1217
1218
1219
1220





37
CD8B319
GYSFTAYY
INPSAGGT
ARWTNPFDY
QNVGTA
SAS
QQYNNYLT




1249
1250
1251
1252
1253
1254





38
CD8B194
GYTFTSYW
IYPGSSST
ARELGPYYRYSAMVY
QNVGTA
SAS
QQYSSYPFT




1283
1284
1285
1286
1287
1288





39
CD8B231
GYTFTNYW
IDPSDSET
ASGLTGTGHY
QDINIY
HTS
QQDNTLPYT




1317
1318
1319
1320
1321
1322





40
CD8B238
GYTFTDYS
IYTYSGGA
ARDSSDYEFAY
QDIKSY
RAN
LQYDEFRT




1351
1352
1353
1354
1355
1356





41
CD8B255
GFSLNTSGMG
IFWDDDK
ARRDGYGDYAYFDV
ENIYSD
AAT
QHFWGTPWT




1385
1386
1387
1388
1389
1390





42
CD8B324
GYTSTSHW
IYPGSSST
ARHSPGHRDYAMDY
QNVGTA
SAS
QQYSTYPLT




1419
1420
1421
1422
1423
1424





43
CD8B337
GFSLSTSGMG
IFWDDDR
ARRVGYGDYAYFDV
ENIYSD
AAT
QHFWGTPWT




1453
1454
1455
1456
1457
1458





44
CD8B344
GYSFTNYW
IYPGSDSS
AREEADYRYTWFVY
QNVGTA
SAS
QQYSSYPLT




1487
1488
1489
1490
1491
1492





45
CD8B264
GYSFTSYW
IYPGSSST
AREEYSYKSSWFAY
QNVGTA
SAS
QQYSTYPYT




1521
1522
1523
1524
1525
1526





46
CD8B318
GYTFTSYW
IYPGSSSS
AREEYSYFPSWFAY
QNVGTA
SAS
QQYSTYPFT




1555
1556
1557
1558
1559
1560





47
CD8B333
GYSFASFW
IYPGSSST
AREEYSYKSSWFAY
QNVGTA
SAS
QQYSTYPYT




1589
1590
1591
1592
1593
1594





48
CD8B366
GFNIKDDY
IDPANGNP
ARDDEGYYYFDV
KSISKY
SGS
QQHNEYPLT




1623
1624
1625
1626
1627
1628





49
CD8B368
GYTFTSYW
IYPFSSST
AREEFSHYPSWFAY
QNVGIA
SAS
QQYSTDPYT




1657
1658
1659
1660
1661
1662





50
CD8B370
GYTFTSYW
IYPGSSST
TRELGAYYHYSAMDY
QNVGTA
SAS
QQYSIYPFT




1691
1692
1693
1694
1695
1696





51
CD8B186
GYIFTSYW
INPSSGYA
ARRVFYGDSWFAY
GNIHNY
NAK
QHFWSTTWT




1725
1726
1727
1728
1729
1730





52
CD8B190
GYSFTSYY
IDPFNGNT
ASPNSNYVGTWFAY
QNINVW
KAS
QQGQSFPFT




1759
1760
1761
1762
1763
1764





53
CD8B192
GYTFTDYY
INPYNGGT
ARNYGAMDS
GNIHNY
NAK
QHFWITPPT




1793
1794
1795
1796
1797
1798





54
CD8B193
GYKFTDYY
INPNGGGT
ARTSGTDWYFDV
QNVGTA
SAS
QQYSSYPFT




1827
1828
1829
1830
1831
1832





55
CD8B214
GYTFTTAG
INTHAGES
ARSGDYDGSHPFAY
QDIRPY
YTS
QQDNTLPYT




1861
1862
1863
1864
1865
1866





56
CD8B230
GYTFTDYY
INPNGGGT
ARTSGTDWYFDV
QNVGTA
STS
QQYSIYPFT




1895
1896
1897
1898
1899
1900





57
CD8B245
GFTFTDYY
SRNKGNGYTT
ARTVTGTLFYYALDY
ENIYSY
NAK
QHHYGTPLT




1929
1930
1931
1932
1933
1934





58
CD8B248
GYTFTTYT
INPSSGYT
ARLWAY
QSLVHSSGNTY
KGS
SQSTHVPFT




1963
1964
1965
1966
1967
1968





59
CD8B250
GFSLSNYV
IWTDGST
ARNNGYFPAFFAY
QNVDTD
SAS
QQYNSYPLT




1997
1998
1999
2000
2001
2002





60
CD8B254
GYTFSSYW
IYPGSGST
ARESITTRITPFDH
QSLVHSSGNTY
KGS
SQSTHVPFT




2031
2032
2033
2034
2035
2036





61
CD8B261
GYTFNSYW
IYPGSSST
ARELGGYYRYNAMDY
QDINRY
RAN
LQYDEFPYT




2065
2066
2067
2068
2069
2070





62
CD8B311
GYTFTSYW
IHPNSGST
ARCGYDGAWFAY
QGISNC
YTS
QQYSKVPYT




2099
2100
2101
2102
2103
2104





63
CD8B340
GYTFTNYW
IDPSDTFT
ARGDWDRDWYFDV
QSLLYSDGKTY
LVS
LQATHFPHT




2133
2134
2135
2136
2137
2138





64
CD8B362
GFNIKDTY
IDPANGHT
AIRFAY
HEISGY
AAS
LQYSSYPYT




2167
2168
2169
2170
2171
2172









1.2: Evaluation of Binding to Human CD8+ T Cells and Biophysical Characterization of CD8 Antibodies


Cell binding. Twenty nM antibody was incubated with human pan T cell in assay media (RPMI 1640+1000 HI FBS+ Pen/strep) for 1 hour at 37° C. Secondary antibodies were A647-conjugated goat anti human IgG Fc antibody at 2 μg/mL, and A488-conjugated mouse anti-human CD4 at 1 Hg/mL in staining buffer. Live cells were also gated based on OKT8 control mAb binding. Percent CD8 positive population was calculated by percentage of CD8-positive cell count/live cell count. Results are shown in Table 8 and are reported as Geomean ratios from CD4-negative population (00 CD8-positive population).


Cross-interaction chromatography (CIC): CIC was conducted as previously described (Jacobs et al. (2010) Pharm. Res. 27(1):65-71). Results are shown in Table 8.


Thermal unfolding and aggregation (Tm/Tagg): Thermal unfolding and aggregation was measured 20° C.-95° C. in 1 C/min ramp using Nanodsf Nanotemper's, Prometheus NT.48 instrument. Samples of 20 μL (0.2 mg/mL) in PBS buffer were transferred to 384-well plate in duplicate.


Data was analyzed using PR.THERMCONTROL software. Results are shown in Table 8.









TABLE 8







CD8 Antibody Stability and Binding to Human Pan T Cells














Cell Binding







to Human
















PanT
















Signal/







Background
CIC















(of CD4
Peak
Protein Stability














negative
Retention
Tm1
Tagg


#
Protein Name
population)
Time
(° C.)
(° C.)















1
CD8B191
2440
4.32
70.3
76.6


2
CD8B226
1752
4.34
70.2
78.0


3
CD8B259
1934
4.41
70.5
76.8


4
CD8B298
306
4.29
70.6
76.2


5
CD8B342
1324
4.27
67.5
68.7


6
CD8B364
1562
4.24
65.3
70.7


7
CD8B200
1990
4.23
69.3
82.3


8
CD8B247
1646
4.31
70.1
77.4


9
CD8B265
2076
4.39
70.3
79.0


10
CD8B270
2497
4.32
70.1
79.7


11
CD8B213
827
4.51
67.8
69.9


12
CD8B240
1312
4.30
70.0
81.5


13
CD8B361
1051
4.65
71.1
74.4


14
CD8B246
1112
4.47
60.9
63.1


15
CD8B268
1173
4.44
69.6
72.4


16
CD8B271
911
4.34
69.1
80.4


17
CD8B273
938
4.27
73.0
76.9


18
CD8B288
934
4.32
71.0
73.5


19
CD8B292
910
4.23
68.1
69.2


20
CD8B303
1182
4.37
70.2
79.9


21
CD8B304
923
4.43
64.4
66.4


22
CD8B312
1087
4.29
71.3
78.0


23
CD8B347
1201
4.30
71.1
73.1


24
CD8B350
537
4.61

81.3


25
CD8B356
777
4.46
73.9
76.7


26
CD8B369
685
5.83
67.4
76.2


27
CD8B371
64
4.29
69.1
75.0


28
CD8B182
1490
4.58
70.7
77.8


29
CD8B205
655
4.77
68.9
72.2


30
CD8B223
489
4.46
68.3
74.3


31
CD8B234
856
5.16
67.7
69.0


32
CD8B251
37
5.30
69.4
73.0


33
CD8B269
26
4.28
69.8
81.4


34
CD8B290
1155
4.48
60.5
72.0


35
CD8B310
29
4.32
70.7
78.7


36
CD8B352
827
5.56
72.1
72.6


37
CD8B319
16
4.54
64.8
75.6


38
CD8B194
1972
4.81
69.8
87.2


39
CD8B231
1785
4.19
61.7
77.5


40
CD8B238
1
4.38
69.9
78.3


41
CD8B255
1317
4.25
69.5
78.4


42
CD8B324
1611
4.44
66.9
68.9


43
CD8B337
1983
4.42
68.8
73.2


44
CD8B344
1758
4.26
72.4
75.4


45
CD8B264
122
4.34
70.0
87.2


46
CD8B318
1613
4.78

78.0


47
CD8B333
1843
4.24
70.4
85.0


48
CD8B366
318
4.26
71.8
74.9


49
CD8B368
2007
4.46
70.5
74.7


50
CD8B370
1932
4.69
70.1
86.9


51
CD8B186
36
4.94
65.1
66.4


52
CD8B190
44
4.34
67.9
77.0


53
CD8B192
22
4.84
70.2
79.9


54
CD8B193
641
5.48
70.3
79.6


55
CD8B214
232
4.16
68.1
73.9


56
CD8B230
63
4.88
69.6
82.5


57
CD8B245
44
4.36
66.7
68.3


58
CD8B248
20
4.57
68.4
73.8


59
CD8B250
61
4.42
69.9
79.3


60
CD8B254
23
4.22
65.8
69.8


61
CD8B261
34
4.52
70.5
79.0


62
CD8B311
1
4.28
69.8
78.0


63
CD8B340
8
4.21
64.8
78.0


64
CD8B362
4
4.37
69.6
76.0









Protein binding kinetics by surface plasmon resonance (SPR). All 64 mAbs were captured at 1 μg/ml, with a final capture level ranging from 100 to 400 Rus. Binding to human CD8αβ heterodimer (R&D cat #9358-CD) and hCD8αα homodimer (Table 9) at 11.1 nM, 33.3 nM and 100 nM was measured using a single cycle kinetics method with an association and dissociation of 3 and 10 minutes, respectively, using a flow rate of 50 uL/mL. Biacore 8k was utilized for these assays, and data was analyzed by modeling to a 1:1 binding equation. Results are shown in Table 10.









TABLE 9







CD8αα screening reagents











Protein

SEQ ID


Name
ID
Sequence
NO





Human
hCDaa
MAWVWILLFLMAAAQSIQASQFRVSPLDR
4967


CD8αα

TWNLGETVELKCQVLLSNPTSGCSWLFQP



fused

RGAAASPTFLLYLSQNKPKAAEGLDTQRF



to

SGKRLGDTFVLTLSDFRRENEGYYFCSAL



human

SNSIMYFSHFVPVFLPAKPTTTPAPRPPT



Fc

PAPTIASQPLSLRPEACRPAAGGAVHIRG





LDFACDEPKSCDKTHTCPPCPAPELLGGP





SVFLFPPKPKDTLMISRTPEVICVVVDVS





HEDPEVKFNWYVDGVEVHNAKTKPREEQY





NSTYRVVSVLTVLHQDWLNGKEYKCKVSN





KALPAPIEKTISKAKGQPREPQVYILPPS





RDELTKNQVSLTCLVKGFYPSDIAVEWES





NGQPENNYKTTPPVLDSDGSFFLYSKLTV





DKSRWQQGNVFSCSVMHEALHNHYTQKSL





SLSPGK
















TABLE 10







CD8 Antibody Binding by SPR



























Based




















Protein binding by SPR
on SPR













Protein binding by SPR
to human CD8 αβ heterodimer
Data
















to human CD8αα homodimer
hCD8αβ
hCD8α
hCD8αβ
hCD8αβ
Predicted

















#
Protein Name
ka (1/Ms)
kd (1/s)
KD (M)
Comment
ka (1/Ms)
kd (1/s)
KD (M)
Comment
Epitope




















1
CD8B191
1.23E+05
1.19E−04
9.68E−10

1.23E+05
1.19E−04
9.68E−10

CD8 α


2
CD8B226
1.55E+05
3.42E−04
2.21E−09

1.55E+05
3.42E−04
2.21E−09

CD8 α


3
CD8B259
2.09E+05
2.52E−04
1.20E−09

2.09E+05
2.52E−04
1.20E−09

CD8 α


4
CD8B298
1.32E+05
2.11E−04
1.60E−09

1.32E+05
2.11E−04
1.60E−09

CD8 α


5
CD8B342
1.48E+05
3.84E−04
2.59E−09

1.48E+05
3.84E−04
2.59E−09

CD8 α


6
CD8B364
1.43E+06
3.12E−02
2.19E−08

1.43E+06
3.12E−02
2.19E−08

CD8 α


7
CD8B200
3.32E+06
1.26E−04
3.80E−11

3.32E+06
1.26E−04
3.80E−11

CD8 α


8
CD8B247
2.73E+05
2.81E−04
1.03E−09

2.73E+05
2.81E−04
1.03E−09

CD8 α


9
CD8B265
1.68E+05
1.33E−04
7.91E−10

1.68E+05
1.33E−04
7.91E−10

CD8 α


10
CD8B270
2.41E+06
9.47E−05
3.93E−11

2.41E+06
9.47E−05
3.93E−11

CD8 α


11
CD8B213



Poor Fit, ~5



Poor Fit, ~5
CD8 α







nm



nM



12
CD8B240



Poor Fit, ~1



Poor Fit, ~1
CD8 α







nM



nM



13
CD8B361



Poor Fit, ~1



Poor Fit, ~1
CD8 α







nM



nM



14
CD8B246



Low/No



Low/No
CD8 β







Binding



Binding



15
CD8B268



Low/No



Low/No
CD8 β







Binding



Binding



16
CD8B271



Low/No



Low/No
CD8 β







Binding



Binding



17
CD8B273



Low/No



Low/No
CD8 β







Binding



Binding



18
CD8B288



Low/No



Low/No
CD8 β







Binding



Binding



19
CD8B292



Low/No



Low/No
CD8 β







Binding



Binding



20
CD8B303



Low/No



Low/No
CD8 β







Binding



Binding



21
CD8B304



Low/No



Low/No
CD8 β







Binding



Binding



22
CD8B312



Low/No



Low/No
CD8 β







Binding



Binding



23
CD8B347



Low/No



Low/No
CD8 β







Binding



Binding



24
CD8B350



Low/No



Low/No
CD8 β







Binding



Binding



25
CD8B356



Low/No



Low/No
CD8 β







Binding



Binding



26
CD8B369



Low/No



Low/No
CD8 β







Binding



Binding



27
CD8B371



Low/No



Low/No
CD8 β







Binding



Binding



28
CD8B182



Low/No



Low/No
CD8 β







Binding



Binding



29
CD8B205



Low/No



Low/No
CD8 β







Binding



Binding



30
CD8B223



Low/No



Low/No
CD8 β







Binding



Binding



31
CD8B234



Low/No



Low/No
CD8 β







Binding



Binding



32
CD8B251



Low/No



Low/No
CD8 β







Binding



Binding



33
CD8B269



Low/No



Low/No
CD8 β







Binding



Binding



34
CD8B290



Low/No



Low/No
CD8 β







Binding



Binding



35
CD8B310



Low/No



Low/No
CD8 β







Binding



Binding



36
CD8B352



Low/No



Low/No
CD8 β







Binding



Binding



37
CD8B319



Low/No



Low/No
CD8 β







Binding



Binding



38
CD8B194



Poor Fit, ~1



Poor Fit, ~1
CD8 α/β







nM



nM
interface


39
CD8B231



Poor Fit,



Poor Fit,
CD8 α/β







 ~0.5 nM



~0.5 nM
interface


40
CD8B238



Poor Fit,



Poor Fit,
CD8 α/β







 ~200 pM



 ~200 pM
interface


41
CD8B255



Poor Fit, ~1



Poor Fit, ~1
CD8 α/β







nM



nM
interface


42
CD8B324



Poor Fit, ~1



Poor Fit, ~1
CD8 α/β







nM



nM
interface


43
CD8B337



Poor Fit, ~1



Poor Fit, ~1
CD8 α/β







nM



nM
interface


44
CD8B344



Poor Fit, ~5



Poor Fit, ~5
CD8 α/β







nm



nm
interface


45
CD8B264



Poor Fit,



Poor Fit,
CD8 α/β







 ~0.5 nM



 ~0.5 nM
interface


46
CD8B318



Poor Fit, ~1



Poor Fit, ~1
CD8 α/β







nM



nM
interface


47
CD8B333



Poor Fit, ~1



Poor Fit, ~1
CD8 α/β







nM



nM
interface


48
CD8B366



Poor Fit,



Poor Fit,
CD8 α/β







  ~20 nM



  ~20 nM
interface


49
CD8B368



Poor Fit,



Poor Fit,
CD8 α/β







 ~0.5 nM



 ~0.5 nM
interface


50
CD8B370



Poor Fit, ~5



Poor Fit, ~5
CD8 α/β







nm



nm
interface


51
CD8B186



Low/No



Low/No








Binding



Binding



52
CD8B190



Low/No



Low/No








Binding



Binding



53
CD8B192



Low/No



Low/No








Binding



Binding



54
CD8B193



Low/No



Low/No








Binding



Binding



55
CD8B214



Low/No



Low/No








Binding



Binding



56
CD8B230



Low/No



Low/No








Binding



Binding



57
CD8B245



Low/No



Low/No








Binding



Binding



58
CD8B248



Low/No



Low/No








Binding



Binding



59
CD8B250



Low/No



Low/No








Binding



Binding



60
CD8B254



Low/No



Low/No








Binding



Binding



61
CD8B261



Low/No



Low/No








Binding



Binding



62
CD8B311



Low/No



Low/No








Binding



Binding



63
CD8B340



Low/No



Low/No








Binding



Binding



64
CD8B362



Low/No



Low/No








Binding



Binding









Example 2: Production and Characterization of Antibodies that Bind CD4

2.1: Immunization


One group of (N=8) AlivaMab Mouse Kappa mice were immunized on an AMMPD-4 immunization schedule using human CD4 (R&D Systems Cat #10327-CD) and rhesus CD4-HIS (Acro Biosystems, Cat #CD4-C52H7.) IgG specific ELISA titers were assessed on D20, D27 and D34 on both human CD4 and rhesus CD4 recombinant proteins. Additionally, FACS titers were assessed on D27 and D34 on human SKW3 and SKW3:hCD4 Knockout cells to assess cell expressed CD4 IgG titers in the mice. All mice were selected for the hybridoma fusion and were given a final protein immunization containing human and rhesus CD4 protein 3 days before harvesting of splenic and lymph node material for fusion.


2.2: Hybridoma Method


On the day of immunization, mice were euthanized by cervical dislocation and spleens and lymph nodes were aseptically harvested and processed separately into single cell suspensions. Spleen material was resuspended in red blood cell lysis buffer (Sigma Cat #R7757) to lyse red blood cells. Both spleen and lymph node material were enriched for B cells using ADS standard magnetic selection method prior to fusion which is a negative selection protocol that removes unwanted cells in the lymphocyte preparations prior to fusion.


Spleen and lymph node material were mixed with SP2/0 myeloma cells and washed 3 times in electrofusion buffer prior to fusion. Hybridoma fusion was performed by Electrofusion on the NEPAgene ECFG21 cell fusion system using ADS standard fusion conditions. Fused cells are rested for 5 minutes at room temperature before being removed from the fusion chamber and added to fusion media for plating into 384W plates or bulk culture to cryopreserve fusion material. 14×384W plates were seeded with fusion material in HAT containing media for the first hybridoma campaign from 10% of the total fusion material. The remaining 90% of the fused cells were bulk plated in HAT containing media and cryopreserved the following day. Cells were grown for 9 days in 384W plates and then screened by FACS to identify αCD4 IgG producing hybridoma wells.


2.3: Antibody Recovery and Screening Protocols:


FACS cell binding. αCD4 antibody producing hybridomas were identified by cell surface CD4 binding using FACS. For primary screening SKW3 (human T-ALL) was used as the CD4 positive cell line and SKW3 CD4 knockout (KO) as the negative cell line, respectively. SKW3 KO cells were labeled with Tag-it Violet (BioLegend) at RT for 15 min. After removing extra dye by washing cells with FACS buffer (1% BSA/1 mM EDTA/0.05% NaN3 in PBS) equal number of SKW3 and labeled SKW3 CD4 KO cells were combined, washed, and resuspended in FACS buffer at 8E6 cells/6 mL. Hybridoma supernatants (15 μL/well) were transferred to 384 well v-bottom plates. anti-hCD4 mIgG (clone RPA-T4 at 2 μg/mL) as positive staining control and PBS was used as negative staining control. Cells (˜20K/15 μL/well) were added to the supernatant and incubated at 4° C. for 30 minutes. After washing cells with FACS buffer twice mixture of anti-mouse Fcγ (Jackson ImmunoResearch, cat #115-605-071) and anti-human Kappa (Southern Biotech, cat #2061-02) to the cells (15 μL/well) and incubated at 4° C. for 30 minutes. Cells were washed twice before acquired by IQUE3® Flow Cytometer and analyzed with FORECYT® software (Sartorius). Positive wells were selected with the following criteria: Over 2-fold selective binding to SKW3 cell line relative to SKW3 CD4 KO with over 10% signal above background binding with anti-human Kappa. Hybridomas from primary screening positive wells were transferred to 96 well plates.


FACS Confirmation screens were performed for primary screening positive hybridomas using human PBMCs in addition to SKW3/SKW3 CD4 KO cell lines. PBMCs were thawed and resuspended to 8E6/mL in FACS buffer. Hybridoma supernatants (25 μL/well) were transferred to 96 v-bottom plates. anti-hCD4 mIgG (clone RPA-T4 at 2 μg/mL) and anti-hCD4 mIgG (clone OKT4 at 2 μg/mL) as positive staining controls and FACS buffer was used as negative staining control. PBMCs were added to the 96 well plates (25 μL/well) and incubated at 4° C. for 30 minutes. After washing cells with FACS buffer twice mixture of anti-mouse Fcγ (Jackson ImmunoResearch, cat #115-605-071) and Helix Blue™ (BioLegend) (nucleic acid probe) to the cells (25 μL/well), and incubated at 4° C. for 30 minutes. Cells were washed twice before acquired by IQUE30 Flow Cytometer and analyzed with FORECYT® software (Sartorius). Primary parameter used to assess confirmation was CD4 positive percent of viable cells. CD4 positive cell population was determined by positive staining controls (OKT4 and RPA-T4) described above. SKW3 gMFI binding was used as secondary parameter to assess confirmation. Results are shown in Table 18.


Supernatant screening by Octet (Human CD4). The kinetics of ADS75110 non-clonal supernatants for human CD4 protein was measured using biolayer interferometry on an Octet® Red 384 instrument. Kinetic rate constants and equilibrium dissociation constant were determined using the following reagents: (1) ADS Octet® Red384 (interferometry instrument) Kinetics Assessment Sensors: Anti Mouse IgG Fc Capture (AMC) (Lot 2001073); (2) ADS Octet® Red384 (interferometry instrument) Kinetics Assessment Buffers and Solutions: Kinetics Buffer (PBS, 0.1% BSA, 0.02% Tween-20® (detergent), 0.05% Azide) (Lot 20200331); Regeneration Solution (10 mM Glycine pH 1.7) (Lot 20190612); (3) ADS Octet® Red384 (interferometry instrument) Kinetics Assessment Antibodies and Analytes Used: Recombinant human CD4 (R&D Systems, Cat. 10327-CD, Lot DCSC042004A) with Analyte Concentration Assayed for Binding at 100 nM; and ADS75110 Non-Clonal Supernatant (AlivaMab) Antibody Concentration Used for Loading of 1:3 dilution in kinetics buffer.


Kinetic assessments. Binding kinetics for nonclonal hybridoma supernatants were screened in high throughput against a single concentration of recombinant human CD4 protein (100 nM). Supernatants were diluted 1:3 in kinetics buffer. One hundred microliters of diluted supernatants were added to 384W screening plates. AMC sensors were used to capture hybridoma antibodies from supernatants. Kinetic parameters for ADS75110 nonclonal hybridomas supernatants were determined at 27° C. using the following conditions: Initial AMC Sensor Regeneration of 2×30 s; Initial Baseline of 300 s; Baseline of 120 s; ADS 75110 AMM Ab Loading of 300 s; Baseline of 120 s; Human/rhesus CD4 association of 300 s; Human/rhesus CD4 dissociation 600 s; AMC Sensor Regeneration of 120 s; Total of 33 minutes.


After completion of the kinetic characterization assays, data was analyzed in FORTE BIO analysis software v11. The Y-axis was aligned to the final 5 seconds of the baseline step, with inter-step alignment to the dissociation step. Savitzky-Golay Filtering was used to smooth the data. Kinetic curves were fit to both association and dissociation steps using a 1:1 stoichiometry model. A local fitting was used to calculate single point kinetics for each supernatant for human CD4. Results are shown in Table 19.


Epitope binning by FACS. αCD4 containing hybridoma supernatants were binned against three comparator antibodies by FACS using SKW3 cells, which endogenously express human CD4 protein. Briefly, SKW3 cells were incubated with saturated hybridoma supernatant for 30 minutes at 4° C. The following antibodies were added to the SKW3:hybridoma supernatant mixture and incubated for 30 minutes longer at 4° C.: Mouse αhu CD4 (OKT4)—Alexa Fluor™ 488 (fluorescent dye) Conjugated; Mouse αhu CD4 (RPA-T4)-PE-Dazzle 594 Conjugated; and Human αhu CD4 (OKT4a) (αhu IgG FC Alexa Fluor™ 647 (fluorescent dye) ab used).


Cells were washed with FACS buffer and incubated with secondary antibody Gt α Hu IgG FC Alexa Fluor™ 647 (fluorescent dye) (Jackson Immunologicals, Cat #109-605-170) and Helix NP Blue™ (nucleic acid probe) live dead stain (Biolegend, Cat #425305) for 30 minutes at 4° C. After incubation, cells were washed twice with FACS buffer and data was acquired on Sartorius IQUE3® VBR FACS machine and data was analyzed in FORECYT® software.


The Sartorius IQUE3® FACS machine is a three-laser machine (Violet, Blue, Red) and standard FACS compensation was done for data analysis. Bins were set by competition of the fluorophore conjugated antibodies by a supernatant compared to the binding of fluorophore conjugated antibodies without any competitive supernatant. The three antibodies (clone OKT4, RPA-T4 and OKT4a) have known epitopes and do not compete. Four bins were identified by the single FACS experiment: competitive to OKT4, competitive with RPA-T4, competitive with OKT4a, and non-competitive with the three antibodies. Results are shown in Table 18.


2.4: Antibody Purification from Hybridoma Supernatant


Batch purifications on hybridoma supernatants were conducted to isolate antibodies. Briefly, the hybridoma supernatant salt concentration and pH were increased prior to addition of protein A resin, and this mixture was agitated end-over-end at 4° C. overnight. The supernatant was removed after centrifugation and the resin with bound antibody was transferred into a filter plate and washed four times with HEPES buffered saline (HBS). Antibodies were then eluted with 0.1 M acetic acid pH 3.5 and neutralized with 1 M Tris-Buffer (trisaminomethane) pH 8.0. This mixture was buffer exchanged into HBS using Amicon spin concentrators, 50 kD MWCO. The antibody concentration was determined using a NANODROP™ spectrophotoemeter, and purity was determined by SEC-HPLC and SDS-Page. Results are shown in Table 22.


2.5: Octet Kinetics for Purified AMM Antibodies (Human/Rhesus)


The ability of ADS75110 purified AMM Abs to bind human and rhesus CD4 proteins was measured using biolayer interferometry on an Octet® Red 384 instrument. Kinetic rate constants and equilibrium dissociation constant were using the following reagents: (1) ADS Octet® Red384 (interferometry instrument) Kinetics Assessment Sensors: Anti Mouse IgG Fc Capture (AMC) (Lot 2001073); (2) ADS Octet® Red384 (interferometry instrument) Kinetics Assessment Buffers and Solutions: Kinetics Buffer (PBS, 0.1% BSA, 0.02% Tween-20® (detergent), 0.05% Azide) (Lot 20200331); Regeneration Solution (10 mM Glycine pH 1.7) (Lot 20190612); (3) ADS Octet® Red384 (interferometry instrument) Kinetics Assessment Antibodies and Analytes Used: Recombinant human CD4 (R&D Systems, Cat. 10327-CD, Lot DCSC042004A) with Analyte Concentration Assayed for Binding at 100 nM, 50 nM and 25 nM; Rhesus macaque CD4-HIS (Acro, Cat. CD4-052H7) at 100 nM, 50 nM and 25 nM; and ADS75110 Purified AMM Abs (AlivaMab, Lot 200716) at antibody concentration of 10 μg/ml used for loading. Results are shown in Table 20 (Human CD4 (R&D Systems)) and Table 21 (Rhesus CD4 (Acro Biosystems)).


Kinetic assessments. A three-point, 1:1 serial dilution of human and rhesus CD4 proteins were prepared using kinetics buffer as diluent. ADS75110 purified AMM Abs were diluted to 10 μg/mL in kinetics buffer. 10 mM Glycine pH 1.7, and kinetics buffer were used to regenerate the AMC biosensors. 100 μL of samples and reagents were added to 384W plates (Greneir Bio, C #781209). Kinetic parameters for ADS75110 antibodies were determined using the conditions: Initial AMC Sensor Regeneration of 2×30 s; Initial Baseline of 300 s; Baseline of 120 s; ADS 75110 AMM Ab Loading of 300 s; Baseline of 120 s; Human/rhesus CD4 association of 300 s; Human/rhesus CD4 dissociation 600 s; AMC Sensor Regeneration of 120 s; Total of 33 minutes. An irrelevant antibody derived from the Alivamab mouse was included in the assay as an internal reference control.


After completion of the kinetic characterization assays, data was analyzed in Forte Bio analysis software v11. The Y-axis was aligned to the final 5 seconds of the baseline step, with inter-step alignment to the dissociation step. Savitzky-Golay Filtering was used to smooth the data. Kinetic curves were fit to both association and dissociation steps using a 1:1 stoichiometry model. A global fitting was calculated using the three-point analyte titration to derive a single set of kinetic constants for each antibody against human and rhesus CD4. Results are shown in Table 20 (Human CD4 (R&D Systems)) and Table 21 (Rhesus CD4 (Acro Biosystems)). Clonal supernatant PBMC FACS binding data is also provided in Table 22.


2.6: Sequencing


RNA was extracted from hybridomas using a Qiagen RNeasy kit (Qiagen #74104) according to manufacturer's instructions. Using primer sets specific for heavy chain sequence, kappa light chain sequence, or lambda light chain sequences, a one-step RT-PCR was performed using SuperScript™ III One-Step RT-PCR System with Platinum™ Taq DNA Polymerase (Thermo #12574026) to amplify the entire variable regions. Reactions were done in triplicate for each HC or LC. Products were run on a 2% agarose gel and products were gel extracted and sequenced by Sanger sequencing. Variable sequences for each HC or LC were confirmed if 2 or more nucleotide sequences matched 100%. If sequence was not confirmed, PCR products were placed into TOPO™ vectors (topoisomerase-based cloning) (Thermo #450030) and 10 colonies were sequenced. Open reading frames were identified and sequences were confirmed when nucleotide sequences matched exactly. Antibody variable region sequence analysis is run in house with custom Alivalign sequencing software to identify gene usage. A L234A/L235A/D265S IgG1 vector was made and sequence confirmed (data not shown).


The VH and VL sequences of certain CD4 antibodies are provided in Table 11. The CDRs sequences of certain CD4 antibodies are provided in Table 12 (Kabat), Table 13 (Chothia), Table 14 (AbM), Table 15 (Contact), and Table 16 (IMGT). Additional sequence summaries are provided in Table 17.


2.7: Reformatting of Alivamab Mouse Mabs to Fully Human Mabs


AlivaMab mouse mAbs are readily converted, recombinantly expressed, and purified as any isotype all-human antibody. For example, the nucleotide sequences of the heavy and light chain variable regions of mAbs are transferred and synthesized into DNA and inserted into vectors for recombinant expression in CHO cells. VH was cloned in a frame into a coding sequence for a human IgG1 constant region, and Vκ or VL was cloned in a frame into a coding sequence for a human Cκ or CL region, respectively. Paired HC and LC vectors were transfected into CHO expression of the recombinant fully human antibodies. The fully human IgG1 kappa or lambda mAb forms were purified from tissue culture supernatants using protein A. The fully human versions retain all the characteristics of the parental chimeric AlivaMabs.









TABLE 11







VH and VL Amino Acid Sequences of CD4 Antibodies





















Light Chain



Protein
HC
LC

VLAA
Heavy Chain
AA


#
Name
Isotype
Isotype
VHAA sequence
sequence
AA sequence
sequence

















1
75110_01A06A
IgG1
Kappa
EVQLVESGGGLVQPGG
DIQMTQSPSSV
N/A
N/A






SLRLSCAASGFTFSSY
SASVGDRVSIT








WMSWVRQAPGKGLEWV
CRASQGISSWL








ANINEDGNEKYYVDSV
AWYQQKPGKAP








KGRLTISRDNAKNSLY
KILIYGASSLQ








LQMNSLRAEDTAVYFC
SGVPSRFSGSG








AREGGQWLSLDYWGQG
SGTDFTLTISS








ALVTVSS
LQPEDFATYYC









QQANSFPWTFG









QGTKVEIK








2207
2208
2209
2210





2
75110_01A07A_1
IgG1
Kappa
QVQLQESGPGLVKPSE
DIQMTQSPSSL
N/A
N/A






TLSLTCTVSGGSIINY
SASVGDRVTIT








YWSWIRQPAGKGLEWI
CQASQDIGNYL








GRIYSSGSTNYKSSLK
NWYQQKPGKAP








SRVTMSVDTSKNQFYL
KLLIYDASNLE








KLRSVTAADTAVYYCA
TGVPSRFSGSG








REREAYLYYGLDVWGQ
SGTDFTFTISS








GTTVTVSS
LQPEDLATYYC









QQYDSLPLTFG









GGTKVEIK








2241
2242
2243
2244





3
75110_01C18A
IgG1
Kappa
EVQLVESGGGLIQPGG
DIQMTQSPSSV
N/A
N/A






SLRLSCAASGFTVSSN
SASVGDRVTIT








YMNWVRQAPGKGLEWV
CRASQGINSWL








SVIYAGDNTYSADSVK
AWYQQKPGKAP








GRFTISRDNSNNTLCL
KLLIYAASSLQ








QMNSLRAEDTAVYYCA
SGVPSRFSGSG








REGGTTGAFDIWGQGT
SGTDFTLTISS








MVTVSS
LQPEDFATYYC









QQGNSFPYTFG









QGTKLEIK








2275
2276
2277
2278





4
75110_01D24A
IgG1
Kappa
QVQLQQWGAGLLKPSE
EIQMTQSPSSV
QVQLQQWGAGLLKP
EIQMTQSPSSVSA






TLSLTCAVYGGSFSGY
SASVGDRVTIT
SETLSLTCAVYGGS
SVGDRVTITCRAS






YWSWIRQPPGKGLEWI
CRASQDISNWL
FSGYYWSWIRQPPG
QDISNWLAWYQQK






GEINHSGSTNYNPSLK
AWYQQKPGKAP
KGLEWIGEINHSGS
PGKAPNLLIFAAS






SRVTISVDTSENQFSL
NLLIFAASSLQ
TNYNPSLKSRVTIS
SLQTGVPSRFSGS






KLNSVTAADTAVYYCA
TGVPSRFSGSG
VDTSENQFSLKLNS
GSGTDFTLTISSL






RLVNWFDPWGQGTLVT
SGTDFTLTISS
VTAADTAVYYCARL
QPDDFATYYCQQA






VSS
LQPDDFATYYC
VNWFDPWGQGTLVT
NSFPYSFGQGTNL







QQANSFPYSFG
VSSASTKGPSVFPL
GIKRTVAAPSVFI







QGTNLGIK
APSSKSTSGGTAAL
FPPSDEQLKSGTA








GCLVKDYFPEPVTV
SVVCLLNNFYPRE








SWNSGALTSGVHTF
AKVQWKVDNALQS








PAVLQSSGLYSLSS
GNSQESVTEQDSK








VVTVPSSSLGTQTY
DSTYSLSSTLTLS








ICNVNHKPSNTKVD
KADYEKHKVYACE








KKVEPKSCDKTHTC
VTHQGLSSPVTKS








PPCPAPEAAGGPSV
FNRGEC








FLFPPKPKDTLMIS









RTPEVTCVVVSVSH









EDPEVKFNWYVDGV









EVHNAKTKPREEQY









NSTYRVVSVLTVLH









QDWLNGKEYKCKVS









NKALPAPIEKTISK









AKGQPREPQVYTLP









PSRDELTKNQVSLT









CLVKGFYPSDIAVE









WESNGQPENNYKTT









PPVLDSDGSFFLYS









KLTVDKSRWQQGNV









FSCSVMHEALHNHY









TQKSLSLSPGK







2309
2310
2311
2312





5
75110_01E08A
IgG1
Kappa
EVQLVESGGGLVQPGG
EIVLTQSPGTL
N/A
N/A






SLRLSCAASGFTFNNY
CLSPGERATLS








DMHWVRQATGKGLEWV
CRASQSVSSSY








STIGTAGDTYYPASVK
LAWYQQKPGQA








GRFTIYRENAKNSLYL
PRLLIYGASSR








QMNSLRAGDTAVYYCA
ATGIPDRFSGS








RGGDYYYGMDVWGQGT
GSGTDFTLTIS








TVTVSS
RLEPEDFAVYY









CQQFGSSPFTF









GPGTKVDIK








2343
2344
2345
2346





6
75110_01G11A
IgG1
Kappa
EVQLVESGGGLVQPGG
EIVLTQSPGTL
N/A
N/A






SLRLSCAASGFTFSSY
SLFPGERATLS








DMHWVRQATGKGLEWV
CRASQNTYSSY








STIGTAGDTYYPGSVK
LAWYQQKPGQA








GRFTISRENARNSLFL
PRLLIYGASNR








QMNSLRAGDTAVYYCA
ATGIPDRFSGS








RGGDYYYGMDVWGQGT
GSGTDFTLTIS








TVTVSS
RLEPEDFAVYY









CQQHGTSPFTF









GPGTKVDIK








2377
2378
2379
2380





7
75110_01H18A
IgG1
Kappa
QVQLQQWGAGLLKPSE
DIQMTQSPSSV
N/A
N/A






TLSLTCAVYGGSFSGY
SASVGDRVTIT








YWSWIRQSPGKGLEWI
CRASQGISSWL








GEINQSGSTNYNPSLK
AWYQQKPGKAP








SRVTISVDTSKNQFSL
KLLIYAASSFQ








KLSSVTAADTAVYYCA
SGVPSRFSGSG








RVINWFDSWGQGTLVT
SGTDFTLTISS








VSS
LQTEDFATYYC









QQANSFPYTFG









QGTRLEIK








2411
2412
2413
2414





8
75110_01J09A
IgG1
Kappa
EVQLVESGGGLVQPGG
DIQMTQSPSSV
EVQLVESGGGLVQP
DIQMTQSPSSVSA






SLRLSCVASGFTFSSY
SASVGDRVTIN
GGSLRLSCVASGFT
SVGDRVTINCRAS






WMSWVRQAPGKGLEWV
CRASQGISSWL
FSSYWMSWVRQAPG
QGISSWLAWYQQK






ANTKEDGSDKYYVDSV
AWYQQKPGKAP
KGLEWVANTKEDGS
PGKAPNLLIFGAS






KGRFTICRDNAKNSLY
NLLIFGASSLQ
DKYYVDSVKGRFTI
SLQSGVPSRFSGS






LQMNSLRAEDTAVYYC
SGVPSRFSGSG
CRDNAKNSLYLQMN
GFGTDFSLTITTL






AREGGQWLALDYWGQG
FGTDFSLTITT
SLRAEDTAVYYCAR
QPEDFATYHCQQA






TLVTVSS
LQPEDFATYHC
EGGQWLALDYWGQG
NSFPWTFGQGTKV







QQANSFPWTFG
TLVTVSSASTKGPS
EIKRTVAAPSVFI







QGTKVEIK
VFPLAPSSKSTSGG
FPPSDEQLKSGTA








TAALGCLVKDYFPE
SVVCLLNNFYPRE








PVTVSWNSGALTSG
AKVQWKVDNALQS








VHTFPAVLQSSGLY
GNSQESVTEQDSK








SLSSVVTVPSSSLG
DSTYSLSSTLTLS








TQTYICNVNHKPSN
KADYEKHKVYACE








TKVDKKVEPKSCDK
VTHQGLSSPVTKS








THTCPPCPAPEAAG
FNRGEC








GPSVFLFPPKPKDT









LMISRTPEVTCVVV









SVSHEDPEVKFNWY









VDGVEVHNAKTKPR









EEQYNSTYRVVSVL









TVLHQDWLNGKEYK









CKVSNKALPAPIEK









TISKAKGQPREPQV









YTLPPSRDELTKNQ









VSLTCLVKGFYPSD









IAVEWESNGQPENN









YKTTPPVLDSDGSF









FLYSKLTVDKSRWQ









QGNVFSCSVMHEAL









HNHYTQKSLSLSPG









K







2445
2446
2447
2448





9
75110_01J17A
IgG1
Kappa
EVQLVESGGGLVQPGG
EIVLAQSPGTL
N/A
N/A






SLRLSCAASGFTFSSY
SLSPGERATLS








DMHWVRQGTGKGLEWV
CRASQSVYISY








STIGTADDTYYPGSVK
LAWYQQKPGQA








GRFTISRENAENSLYL
PRLLIYGASSR








QMNSLRAGDTAVYYCA
ATGIPDRFSGS








RGGDYYYGMDVWGQGT
GSGTDFTLTIT








TVTVSS
RLEPEDFAVYY









CQQFGSSPFTF









GPGTKVDFK








2479
2480
2481
2482





10
75110_01K10A
IgG1
Kappa
EVQLVESGGALVQPGG
EIVLTQSPDTL
EVQLVESGGALVQP
EIVLTQSPDTLSL






SLRLSCAASGFTFRNY
SLSPGERATLS
GGSLRLSCAASGFT
SPGERATLSCRAS






DMHWVRQATGKGLEWV
CRASQSLSSVY
FRNYDMHWVRQATG
QSLSSVYLAWYQQ






STIGTAGDTYYPGSVK
LAWYQQKPGQA
KGLEWVSTIGTAGD
KPGQAPRLLIYGA






GRFTISRENAKNSLYL
PRLLIYGASSR
TYYPGSVKGRFTIS
SSRATGIPDRFSG






QMNSLRAGDTAVYYCA
ATGIPDRFSGT
RENAKNSLYLQMNS
TGSGTDFTLTISR






RGGDYYYGMDVWGQGT
GSGTDFTLTIS
LRAGDTAVYYCARG
LEPEDFAVYYCQQ






TVTVSS
RLEPEDFAVYY
GDYYYGMDVWGQGT
YGSSPFTFGPGTK







CQQYGSSPFTF
TVTVSSASTKGPSV
VDIKRTVAAPSVF







GPGTKVDIK
FPLAPSSKSTSGGT
IFPPSDEQLKSGT








AALGCLVKDYFPEP
ASVVCLLNNFYPR








VTVSWNSGALTSGV
EAKVQWKVDNALQ








HTFPAVLQSSGLYS
SGNSQESVTEQDS








LSSVVTVPSSSLGT
KDSTYSLSSTLTL








QTYICNVNHKPSNT
SKADYEKHKVYAC








KVDKKVEPKSCDKT
EVTHQGLSSPVTK








HTCPPCPAPEAAGG
SFNRGEC








PSVFLFPPKPKDTL









MISRTPEVTCVVVS









VSHEDPEVKFNWYV









DGVEVHNAKTKPRE









EQYNSTYRVVSVLT









VLHQDWLNGKEYKC









KVSNKALPAPIEKT









ISKAKGQPREPQVY









TLPPSRDELTKNQV









SLTCLVKGFYPSDI









AVEWESNGQPENNY









KTTPPVLDSDGSFF









LYSKLTVDKSRWQQ









GNVFSCSVMHEALH









NHYTQKSLSLSPGK







2513
2514
2515
2516





11
75110_01L08A
IgG1
Kappa
QVQLQESGPGLVKPSE
DIQMTQSPSSL
N/A
N/A






TLSLTCTVSGGSISHY
SASVGDRVTIT








YWSWIRQPPGKGLEWI
CQASQDISNYL








GYIHYSGTTNYNPSLK
NWYQQKPGKAP








SRVTISVDTSKNQLSL
KLLIYDASNLE








KLRSVTAADTAVYYCA
TGVPSRFSGSG








RDQGFSSGGMDVWGQG
SGTDFTFAISS








TTVTVSS
LQPEDIATYYC









QQYDNLPLTFG









GGTKVEIK








2547
2548
2549
2550





12
75110_01N04A
IgG1
Kappa
EVQLVESGGGLVQPGG
EIMLTQSPGTL
N/A
N/A






SLRLSCAASGFTFSNY
SLSPGERATLS








DMHWVRQATGKGLEWV
CRASQSVSSVY








STIGTAGDTYYPGSVK
LAWYQQKPGQA








GRFTISRENAKNSLYL
PRLLIYGASSR








QMNSLRAGDTAVYYCA
ATGIPDRFSGS








RGGDFYYGLDVWGQGT
GSGTDFTLTIS








TVTVSS
RLEPEDFAVYY









CQQYGSSPFTF









GPGTKVDFK








2581
2582
2583
2584





13
75110_02E08A
IgG1
Kappa
QVQLQESGPGLVKPSE
DIQMTQSPSAM
N/A
N/A






TLSLTCTVSGGSISTY
SASVGDRVTIT








YWTWIRQPAGKGLEWI
CRASQDISNYL








GRVYTSGDTNYNPSLK
AWFQQKPGKVP








SRVAMSLDTSKNQFSL
KRLIYAASSLQ








KLSSVTAADTAVYYCA
SGVPSRFSGSG








RDSGALYSWNYGDAFD
SGTEFTLTISS








IWGQGTMVTVSS
LQPEDFATYYC









LQHNSYPRTFG









QGTKVEIK








2615
2616
2617
2618





14
75110_02E22A
IgG1
Kappa
QVQLQESGPGLVKPSE
DIQMTQSPSSL
N/A
N/A






TLSLTCTVSGGSISSF
SASVGDRVTIT








YWSWIRQPAGKGLEWI
CQASHDISNYL








GRIYTSGSTNYNPSLK
NWYQQKPGKAP








SRVTMSVDTSKNQFSL
KLLIFDASTLE








KLSSVTAADTAVYYCA
TGVPSRFSGSG








RELEKRNYYGMDVWGQ
SGTYFTFTIRS








GTTVTVSS
LQPEDIATYYC









QQYDSLPLTFG









GGTKVEIK








2649
2650
2651
2652





15
75110_02I16A
IgG1
Kappa
QVQLQQWGAGLLKPSE
DIQMTQSPSSV
N/A
N/A






TLSLTCDVYGGSFSGY
SASVGDRVTIT








YWTWIRQPPGKGLEWI
CRASQDIANWL








GEINHSGTTNSNPSLK
AWYQQKPGKAP








SRVTISVDTSKSQFSL
QLLIYAASSLL








RLSSVTAADTAVYFCT
GGVPSRFSGSG








RELNWFDPWGQGTLVT
SGADFTLTISS








VSS
LHPEDFATYYC









QQANSFPYTFG









QGTKLEIK








2683
2684
2685
2686





16
75110_02I18A
IgG1
Kappa
EVQVVESGGGLVQPGG
EIVLTQSPGTL
N/A
N/A






SLRLSCAASGFTFSSY
SLSPGERATLS








DMHWVRQATGKGLEWV
CRASQSVSSSY








STIGTAGDTYYPGSVK
LAWYQQKPGQS








GRFTISRENAKNSLYL
PRLLIHGASSR








QMNSLRAGDTAVYYCA
ATGIPDRVSGS








RGGYYYYGMDVWGQGT
GSGTDFTLTIS








TVTVSS
RLEPEDFAVYY









CQQYGSSPFTF









GPGTKVDIK








2717
2718
2719
2720





17
75110_02K11A
IgG1
Kappa
QVQLQESGPGLVKPSQ
EIVLTQSPGTL
N/A
N/A






TLSLTCTVSGGSISSG
SLSPGEGATLS








FYYWTWIRQHPGKGLE
CRASQSVSTSY








WIGYISYSGNTYYNPS
LAWYQQKPGQA








FKSRLTISVDTSKSQF
PRLLIYGASSR








SLKLSSVTAADTAVYY
ATGIPDRFSGS








CARDRPSNFDAFDIWG
GSGTDFTLTIS








QGTMVTVSS
RLEPEDFAVYY









CQQYGRSPLTF









GPGTKVDIK








2751
2752
2753
2754





18
75110_02N15A
IgG1
Kappa
EVQLVESGGGLVQPGG
DIQMTQSPSSV
N/A
N/A






SLRLSCAASGFTFSSY
SASVGDRVTIT








WMSWVRQAPGKGLEWV
CRASQGISSWL








ANINEDGNEKYYVDSV
AWYQQKPGKAP








KGRFTISRDNAKNSLF
KFLISGASSLQ








LQMNSLRAEDTAVYFC
SGVPSRFSGSG








AREGGQWLALDHWGQG
SGTDFTLTISS








ALVTVSS
LQPEDFATYYC









QQANSFPWTFG









QGTKVEFK








2785
2786
2787
2788





19
75110_03B16A
IgG1
Kappa
EVQLVESGGGLVQPGG
DIQMTQSPSSV
N/A
N/A






SLRLSCAASGFTFSSY
SASVGDRVNIT








WMSWVRQAPGKGLEWV
CRASQGIRSWL








ANINEDGSEKNYVDSV
AWYQQKPGKTP








KGRFTISRDNAKNSLC
KLLICGASSLQ








LQLNSLRAEDTAVYHC
SGVPSRFSGSG








AREGGQWLALDYWGQG
SGTDFTLTISS








TLVTVSS
LQPEDFATYYC









QQANSFPWTFG









QGTTVEIK








2819
2820
2821
2822





20
75110_03C01A
IgG1
Kappa
QVQLQQWGAGLLKPSE
DIQMTQSPSSV
N/A
N/A






TLSLTCAVYGGSFSGY
SASVGDRVTIT








YWSWIRQSPGKGLEWI
CRASQGISSWL








GEINQSGSTNYNPSLK
AWYQQKPGNAP








SRVTISVDTSKDQFSL
KLLIYDASSFQ








KLSSVTAADTAVYYCA
SGVPSRFSGSG








RVINWFDSWGQGSLVT
SGTDFTLTISS








VSS
LQTEDFATYYC









QQANSFPYTFG









QGTKLEIK








2853
2854
2855
2856





21
75110_03D16A
IgG1
Kappa
EVQLVESGGGLVQPGG
DIQMTQSPSSV
N/A
N/A






SLRLSCAASGFTFSSY
SASVGDRVTIT








WMSWVRQAPGKGLEWV
CRASQGISSWL








ANINQDGGEKYYVDSV
TWYQQKPGKAP








KGRFTISRDNAKNSLY
KFLIYAASSLQ








LQMNSLRAEDTAVYYC
SGVPSRFSGSG








VREGGQWLALDYWGQG
FGTDFTLTISS








TLVTVSS
LQPEDFATYYC









QQANSFPWTFG









QGTKVEIK








2887
2888
2889
2890





22
75110_03I08A
IgG1
Kappa
QVQLQESGPGLVKPSE
EIVLTQSPGTL
N/A
N/A






TLSLTCTVSGGSISSY
SLSPGERATLS








YWSWIRQPPGKGLEWI
CRASQSVSSTY








GYIYYSGSTNYNPSLK
LAWYQQKPGQA








SRVTISVDTSKNQFSL
PRLLIYGSSSR








KLSSVTAADTAVYYCA
ATGIPDRFSGS








REGEQWFYGLDVWGQG
GSGTDFTLTIS








TTVTVSS
RLEPEDFAVYY









CQQYGNSFPIT









FGQGTRLEIK








2921
2922
2923
2924





23
75110_03I23A
IgG1
Kappa
QVQLQESGPGLVKPSE
DIQMTQSPSSL
N/A
N/A






TLSLTCTASGGSITSY
SASVGDRVTIT








YWNWIRQPAGKGLEWI
CQASQDISNYL








GRIYTSGSTNYNPSLK
NWYQQKPGKAP








SRVTMSVDTSKNQFSL
KLLIYDASNLE








KLSSVTAADTAVYYCA
TGVPSRFSGSG








RDPGYSDAFNIWGQGT
SGTDFTFAISS








MVTVSS
LQPEDIATYYC









QQCDNLPLTFG









GGTKVEIK








2955
2956
2957
2958





24
75110_03L12A
IgG1
Kappa
QVQLQQWGAGLLKPSE
DIQMTQSPSSV
QVQLQQWGAGLLKP
DIQMTQSPSSVSA






TLSLTCAVYGGSFSGY
SASVGDRVTIT
SETLSLTCAVYGGS
SVGDRVTITCRAS






YWSWIRQPPGKGLEWI
CRASQDISNWL
FSGYYWSWIRQPPG
QDISNWLAWYQQK






GEINHSGSTNYNPSLK
AWYQQKPGKAP
KGLEWIGEINHSGS
PGKAPKLLIFAAS






SRVTISVDTSENQFSL
KLLIFAASSLQ
TNYNPSLKSRVTIS
SLQSGVPSRFSGS






TLISVTAADTAVYYCV
SGVPSRFSGSG
VDTSENQFSLTLIS
GSGTDFTLTISSL






RLINWFDPWGQGTLVT
SGTDFTLTISS
VTAADTAVYYCVRL
QPDDFATYYCQQA






VSS
LQPDDFATYYC
INWFDPWGQGTLVT
NSFPYTFGQGTNL







QQANSFPYTFG
VSSASTKGPSVFPL
GIKRTVAAPSVFI







QGTNLGIK
APSSKSTSGGTAAL
FPPSDEQLKSGTA








GCLVKDYFPEPVTV
SVVCLLNNFYPRE








SWNSGALTSGVHTF
AKVQWKVDNALQS








PAVLQSSGLYSLSS
GNSQESVTEQDSK








VVTVPSSSLGTQTY
DSTYSLSSTLTLS








ICNVNHKPSNTKVD
KADYEKHKVYACE








KKVEPKSCDKTHTC
VTHQGLSSPVTKS








PPCPAPEAAGGPSV
FNRGEC








FLFPPKPKDTLMIS









RTPEVTCVVVSVSH









EDPEVKFNWYVDGV









EVHNAKTKPREEQY









NSTYRVVSVLTVLH









QDWLNGKEYKCKVS









NKALPAPIEKTISK









AKGQPREPQVYTLP









PSRDELTKNQVSLT









CLVKGFYPSDIAVE









WESNGQPENNYKTT









PPVLDSDGSFFLYS









KLTVDKSRWQQGNV









FSCSVMHEALHNHY









TQKSLSLSPGK







2989
2990
2991
2992





25
75110_04B08A
IgG1
Kappa
QVQLVESGGGVVQPGR
AIQMTQSPSSL
QVQLVESGGGVVQP
AIQMTQSPSSLSA






SLRLSCTASGFNFINY
SASVGDRVTIT
GRSLRLSCTASGFN
SVGDRVTITCRAS






GIHWVRQAPGKGLEWV
CRASQDIRNDL
FINYGIHWVRQAPG
QDIRNDLGWYQQK






TIIWYDGSKKYYADSV
GWYQQKPGKAP
KGLEWVTIIWYDGS
PGKAPNLLIYAAS






KGRFAISRDNSKNTLY
NLLIYAASNLQ
KKYYADSVKGRFAI
NLQSGVPSRFSGS






LQMNSLRAEDTAVYYC
SGVPSRFSGSG
SRDNSKNTLYLQMN
GSGTDFTLTISSL






AREDDWNDGLAYWGQG
SGTDFTLTISS
SLRAEDTAVYYCAR
QPEDFATYYCLQD






TLVTVSS
LQPEDFATYYC
EDDWNDGLAYWGQG
SNYPRTFGQGTKV







LQDSNYPRTFG
TLVTVSSASTKGPS
EIKRTVAAPSVFI







QGTKVEIK
VFPLAPSSKSTSGG
FPPSDEQLKSGTA








TAALGCLVKDYFPE
SVVCLLNNFYPRE








PVTVSWNSGALTSG
AKVQWKVDNALQS








VHTFPAVLQSSGLY
GNSQESVTEQDSK








SLSSVVTVPSSSLG
DSTYSLSSTLTLS








TQTYICNVNHKPSN
KADYEKHKVYACE








TKVDKKVEPKSCDK
VTHQGLSSPVTKS








THTCPPCPAPEAAG
FNRGEC








GPSVFLFPPKPKDT









LMISRTPEVTCVVV









SVSHEDPEVKFNWY









VDGVEVHNAKTKPR









EEQYNSTYRVVSVL









TVLHQDWLNGKEYK









CKVSNKALPAPIEK









TISKAKGQPREPQV









YTLPPSRDELTKNQ









VSLTCLVKGFYPSD









IAVEWESNGQPENN









YKTTPPVLDSDGSF









FLYSKLTVDKSRWQ









QGNVFSCSVMHEAL









HNHYTQKSLSLSPG









K







3023
3024
3025
3026





26
75110_04D20A
IgG1
Kappa
QVQLQESGPGLVKPSE
DIQMTQSPSSL
N/A
N/A






TLSLTCTVSNGSISDY
SASVGDRVTIT








YWSWIRQPAGKGLEWI
CQASQDISNYL








GRIYTSGSTNYNPSLK
NWYQQKPGKAP








SRITMSVDTSKNQFSL
KLLIYAASNLE








ELSSVTAADTAVYYCA
TGVPSRFSGSG








RELERYYFYGVDVWGQ
SGTDFTFTISS








GTTVTVSS
LQPEDIATYYC









QQYDSLPLTFG









GGTKVEIK








3057
3058
3059
3060





27
75110_04F22A
IgG1
Kappa
EVQLVESGGGLVQPGG
EIVLTQSPGTL
EVQLVESGGGLVQP
EIVLTQSPGTLSL






SLRLSCAASGFTFSSY
SLSPGERATLS
GGSLRLSCAASGFT
SPGERATLSCRAS






DIHWVRQATGKGLEWV
CRASQSVYSSY
FSSYDIHWVRQATG
QSVYSSYLAWYQQ






STIGTAGDTYYPGSVK
LAWYQQKPGQA
KGLEWVSTIGTAGD
KPGQAPRLLIYGA






GRFTISRENAKNSLYL
PRLLIYGASSR
TYYPGSVKGRFTIS
SSRATGIPDRFSG






QMNSLRAGDTAVYYCA
ATGIPDRFSGS
RENAKNSLYLQMNS
SGSGTDFTLTISR






RGGYYYYGMDVWGQGT
GSGTDFTLTIS
LRAGDTAVYYCARG
LEPEDFAVYYCQQ






TVTVSS
RLEPEDFAVYY
GYYYYGMDVWGQGT
FGTSPFTFGPGTK







CQQFGTSPFTF
TVTVSSASTKGPSV
VDIKRTVAAPSVF







GPGTKVDIK
FPLAPSSKSTSGGT
IFPPSDEQLKSGT








AALGCLVKDYFPEP
ASVVCLLNNFYPR








VTVSWNSGALTSGV
EAKVQWKVDNALQ








HTFPAVLQSSGLYS
SGNSQESVTEQDS








LSSVVTVPSSSLGT
KDSTYSLSSTLTL








QTYICNVNHKPSNT
SKADYEKHKVYAC








KVDKKVEPKSCDKT
EVTHQGLSSPVTK








HTCPPCPAPEAAGG
SFNRGEC








PSVFLFPPKPKDTL









MISRTPEVTCVVVS









VSHEDPEVKFNWYV









DGVEVHNAKTKPRE









EQYNSTYRVVSVLT









VLHQDWLNGKEYKC









KVSNKALPAPIEKT









ISKAKGQPREPQVY









TLPPSRDELTKNQV









SLTCLVKGFYPSDI









AVEWESNGQPENNY









KTTPPVLDSDGSFF









LYSKLTVDKSRWQQ









GNVFSCSVMHEALH









NHYTQKSLSLSPGK







3091
3092
3093
3094





28
75110_04G02A
IgG1
Kappa
EVQLVESGGGLVKPGG
DIVMTQSPDSL
N/A
N/A






SLRLSCAASGFTFSNA
AVSLGERATIN








WMSWVRQAPGKGLEWV
CKSSQSVLYSS








GRIKSKTDGGTTDYAA
NNKNYLAWYQQ








PVKGRFTISRDDSKNT
KPGQPPKLLFY








LYLQMNSLKTEDTAVY
WASARESGVPD








YCTTGGWFGELWGPFD
RFSGSGSGTDF








IWGQGTMVTVSS
TLTISSLQAED









VALYYCQQYFG









SFPTFGQGTKL









EIK








3125
3126
3127
3128





29
75110_04G16A
IgG1
Kappa
QVQLQESGPGLVKPSQ
EIVLTQSPGTL
QVQLQESGPGLVKP
EIVLTQSPGTLSL






TLSLTCTVSGDSISSG
SLSPGERATLS
SQTLSLTCTVSGDS
SPGERATLSCRAS






YYYWSWIRQHPGKGLE
CRASQSVGSTY
ISSGYYYWSWIRQH
QSVGSTYLAWYQQ






WIGYISYSGSTYYNPS
LAWYQQKPGQA
PGKGLEWIGYISYS
KPGQAPRLLIYGA






LKSRLTISVNTSKNQF
PRLLIYGAFSR
GSTYYNPSLKSRLT
FSRATGIPDRFSG






SLKLSSLTAADTAVYY
ATGIPDRFSGS
ISVNTSKNQFSLKL
SGSGTDFTLTISR






CARDRPSNFDAFDIWG
GSGTDFTLTIS
SSLTAADTAVYYCA
LEPEDFAVYYCQQ






QGTMVTVSS
RLEPEDFAVYY
RDRPSNFDAFDIWG
YGSSPLTFGPGTK







CQQYGSSPLTF
QGTMVTVSSASTKG
VDIKRTVAAPSVF







GPGTKVDIK
PSVFPLAPSSKSTS
IFPPSDEQLKSGT








GGTAALGCLVKDYF
ASVVCLLNNFYPR








PEPVTVSWNSGALT
EAKVQWKVDNALQ








SGVHTFPAVLQSSG
SGNSQESVTEQDS








LYSLSSVVTVPSSS
KDSTYSLSSTLTL








LGTQTYICNVNHKP
SKADYEKHKVYAC








SNTKVDKKVEPKSC
EVTHQGLSSPVTK








DKTHTCPPCPAPEA
SFNRGEC








AGGPSVFLFPPKPK









DTLMISRTPEVTCV









VVSVSHEDPEVKFN









WYVDGVEVHNAKTK









PREEQYNSTYRVVS









VLTVLHQDWLNGKE









YKCKVSNKALPAPI









EKTISKAKGQPREP









QVYTLPPSRDELTK









NQVSLTCLVKGFYP









SDIAVEWESNGQPE









NNYKTTPPVLDSDG









SFFLYSKLTVDKSR









WQQGNVFSCSVMHE









ALHNHYTQKSLSLS









PGK







3159
3160
3161
3162





30
75110_04H17A
IgG1
Kappa
QVQLQESGPGLVKPSE
DVQMTQSPSSL
N/A
N/A






TLSLTCTVSGGSISTY
SASVGGRVTIT








YWSWIRQSAGKGLEWI
CQASQDISNYL








GRIYTSERPNYNPSLK
NWYQQKPGKAP








SRVTMSVDTSKNQFSL
KLLIYYASNLE








KLNSVSAADTAVYYCA
TGVPSRFSGSG








RELERPYYYGMDVWGQ
SGTDFTFTISS








GTTVTVSS
LQPEDFATYYC









QQYDNLPLTFG









GGTKVEIK








3193
3194
3195
3196





31
75110_04K10A
IgG1
Kappa
EVQLVESGGGLVQPGG
DIQMTQSPSSV
N/A
N/A






SLRLSCAASGFTFSSY
SASVGDRVTIT








WMSWVRQAPGKGLEWV
CRASQGISSWL








ANINQDGSEKYYVDSV
AWYQQKPGKAP








KGRFTISRDNAKNSLY
KVLIYGVSSFQ








LQLNSLRAEDTAMYYC
SGVPSRFSGSG








AREGGQWLSLDYWGQG
SGTDFILTISS








TLVTVSS
LQPEDFATYYC









QQANSFPWTFG









QGTKVEIK








3227
3228
3229
3230





32
75110_04P06A
IgG1
Kappa
EVQLVESGGGLVQPGG
EIVLTQSPDTL
N/A
N/A






SLRLSCAASGFTFSNY
SLSPGERATLS








DMHWVRQATGKGLEWV
CRASQSLSSVY








STIGTAGDTYYPGSVK
LAWYQQKPGQA








GRFTISRENAKNSLYL
PRLLIYGASSR








QMNSLRAGDTAVYYCA
ATGIPDRFSGS








RGGDYYYGMDVWGQGT
GSGTDFTLTIN








TVTVSS
RLEPEDFVVYY









CQQYGSSPFTF









GPGTKVDIK








3261
3262
3263
3264





33
75110_04P08A
IgG1
Kappa
QVQLQQWGAGLLKPSE
DIQMTQSPSSV
QVQLQQWGAGLLKP
DIQMTQSPSSVSA






TLSLTCAVYGGSLSGY
SASVGDRVTLT
SETLSLTCAVYGGS
SVGDRVTLTCRAS






YWSWIRQSPGKGLEWI
CRASQDISNWL
LSGYYWSWIRQSPG
QDISNWLAWYQQK






GEINQSGSTNYNPSLK
AWYQQKPGKAP
KGLEWIGEINQSGS
PGKAPKLLIYAAS






SRVTISVDTSKDQFSL
KLLIYAASSLQ
TNYNPSLKSRVTIS
SLQSGVPSRFSGS






RLTSVTAADTAVYYCT
SGVPSRFSGSG
VDTSKDQFSLRLTS
GSGTDFTLTISSL






RVLNWFDPWGRGTLVT
SGTDFTLTISS
VTAADTAVYYCTRV
QTEDFATYYCQQA






VSS
LQTEDFATYYC
LNWFDPWGRGTLVT
NSFPYTFGQGTKL







QQANSFPYTFG
VSSASTKGPSVFPL
EIKRTVAAPSVFI







QGTKLEIK
APSSKSTSGGTAAL
FPPSDEQLKSGTA








GCLVKDYFPEPVTV
SVVCLLNNFYPRE








SWNSGALTSGVHTF
AKVQWKVDNALQS








PAVLQSSGLYSLSS
GNSQESVTEQDSK








VVTVPSSSLGTQTY
DSTYSLSSTLTLS








ICNVNHKPSNTKVD
KADYEKHKVYACE








KKVEPKSCDKTHTC
VTHQGLSSPVTKS








PPCPAPEAAGGPSV
FNRGEC








FLFPPKPKDTLMIS









RTPEVTCVVVSVSH









EDPEVKFNWYVDGV









EVHNAKTKPREEQY









NSTYRVVSVLTVLH









QDWLNGKEYKCKVS









NKALPAPIEKTISK









AKGQPREPQVYTLP









PSRDELTKNQVSLT









CLVKGFYPSDIAVE









WESNGQPENNYKTT









PPVLDSDGSFFLYS









KLTVDKSRWQQGNV









FSCSVMHEALHNHY









TQKSLSLSPGK







3295
3296
3297
3298





34
75110_05A11A
IgG1
Kappa
EVQLVESGGGLVKPGG
DIQMTQSPSSL
N/A
N/A






SLTLSCAASGFTFSNT
SASVGDRVTIT








WMSWVRQAPGKGLEWV
CQASQDISNYL








GRIKSKIDGGTTDYAA
NWYQQKPGKAP








PVKGRFTISRDDSKNT
KLLIYDTSNLE








LYLQMNSLKTEDTAVY
AGVPSRFSGSG








YCTTSGTYSSGWGLFD
SGTHFTLTISS








YWGQGTLVTVSS
LQPEDIATYYC









QQYDNLPFTFG









GGTRVEIK








3329
3330
3331
3332





35
75110_05B13A
IgG1
Kappa
QVLLEQWGAGLLKPSE
DIQMTQSPSSV
N/A
N/A






TLSLTCAVYGGSFSGY
SASVGDRVTIT








YWTWIRQPPGKGLEWI
CRASQDISNWL








GEINHRGSTNYNPSLK
AWYQQKPGKAP








SRVTISIDTSKNQFSL
KLLIFAASSLQ








KVKSVTAADTAMYYCT
SGVPSRFSGSG








RPDSNWFDPWGQGTLV
SGTDFTLTISS








TVSS
LQPEDFATYYC









QQANSFPLTFG









GGTKVEIK








3363
3364
3365
3366





36
75110_05E05A
IgG1
Kappa
QVQLQESGPGLVKPSE
DIVMTQTPLSL
QVQLQESGPGLVKP
DIVMTQTPLSLPV






TLSLTCTVSGGSIGSY
PVTPGEPASIS
SETLSLTCTVSGGS
TPGEPASISCRSS






YWSWIRQPAGKGLEWI
CRSSQSLLDSD
IGSYYWSWIRQPAG
QSLLDSDDGNTYL






GRIYTSGSTNYNPSLK
DGNTYLDWYLQ
KGLEWIGRIYTSGS
DWYLQKPGQSPQL






SRVTMSFDTSKNQFSL
KPGQSPQLLIY
TNYNPSLKSRVTMS
LIYTLSYRASGVP






KLNSVTAADTAVYYCA
TLSYRASGVPD
FDTSKNQFSLKLNS
DRFSGSGSGTDFT






TDGGVGDSLDYWGQGT
RFSGSGSGTDF
VTAADTAVYYCATD
LKISRVEAEDVGV






LVTVSS
TLKISRVEAED
GGVGDSLDYWGQGT
YYCMQHIEFPFTF







VGVYYCMQHIE
LVTVSSASTKGPSV
GPGTKVDIKRTVA







FPFTFGPGTKV
FPLAPSSKSTSGGT
APSVFIFPPSDEQ







DIK
AALGCLVKDYFPEP
LKSGTASVVCLLN








VTVSWNSGALTSGV
NFYPREAKVQWKV








HTFPAVLQSSGLYS
DNALQSGNSQESV








LSSVVTVPSSSLGT
TEQDSKDSTYSLS








QTYICNVNHKPSNT
STLTLSKADYEKH








KVDKKVEPKSCDKT
KVYACEVTHQGLS








HTCPPCPAPEAAGG
SPVTKSFNRGEC








PSVFLFPPKPKDTL









MISRTPEVTCVVVS









VSHEDPEVKFNWYV









DGVEVHNAKTKPRE









EQYNSTYRVVSVLT









VLHQDWLNGKEYKC









KVSNKALPAPIEKT









ISKAKGQPREPQVY









TLPPSRDELTKNQV









SLTCLVKGFYPSDI









AVEWESNGQPENNY









KTTPPVLDSDGSFF









LYSKLTVDKSRWQQ









GNVFSCSVMHEALH









NHYTQKSLSLSPGK







3397
3398
3399
3400





37
75110_05E13A
IgG1
Kappa
EVQLVESGGDLVKPGG
DIQMTQSPSTL
N/A
N/A






SLRLSCAASGFSFSNA
SASVGDRVTIT








WMSWVRQAPGKGLEWV
CRASQSISSWL








GRVESKTDGGTTDYAA
AWYQQKPGKAP








PVKDRFTISRDDSKYT
MLLIYKASSLE








LYLQMNSLKTEDSAVY
SGVPSRFSGSG








YCTIGGGFGLELYGFF
SGTEFTLTISS








DYWGQGTLVTVSS
LQPDDFATYYC









LQYNSYYTFGQ









GTKLEIK








3431
3432
3433
3434





38
75110_05F19A
IgG1
Kappa
EVQLVESGGGLVQPGG
EIVLTQSPGTL
N/A
N/A






SLRLSCAASGFTFSNY
SLSPGERATLS








DVHWVRQPTGKGLEWV
CRASQSVSSTY








STIGTAGDTYYPGSVK
LAWYQQKPGQA








GRFTISRENAKNSLYL
PRLLIFGASSR








QMNSLRAGDTAVYYCA
ATGIPDRFSGS








RGGYDYYGLDVWGQGT
GSGTDFTLTIS








TVTVSS
RLEPEDFAVYY









CQQYGSSPFTF









GPGTKVDIK








3465
3466
3467
3468





39
75110_05G15A
IgG1
Kappa
QVQLQESGPGLVKPSQ
EIVLTQSPGTL
N/A
N/A






TLSLTCTVSGGSISSG
SLSPGERATLS








GYFWSWIRQHPGKGLE
CRASQSVSSSY








WIGCIYYSGSTYYIPS
LAWYQQKPGQA








LKSRVTISVDTSKNQF
PRLLIYGASSR








SLKLRSVTAADTAVYY
ATGIPDRFSGS








CARDGYDYWYFDLWGR
GSGTDFTLTIS








GTLVTVSS
RLEPEDFAVYY









CQQYGSSPYTF









GQGTKLEIK








3499
3500
3501
3502





40
75110_05K11A
IgG1
Kappa
EVQLVESGGGLVQPGG
EIVLTQSPGTL
N/A
N/A






SLRLSCAASGFTFSSY
SLSPGERVTLS








DMHWVRQPTGKGLEWV
CRASQSVSNTY








STIGTAGDTYYPASVK
LAWYQQKPGQA








GRFTISRENAKNSLYL
PRLLIYGASSR








QMNSLRAGDTAVYYCA
ATGIPDRFSGS








RGGFYYYGMDVWGQGT
GSGTDFTLTIS








TVTVSS
RLEPEDFVVYY









CQQHGSSPFTF









GPGTKVDIK








3533
3534
3535
3536





41
75110_05L07A
IgG1
Kappa
EVQLVESGGGLVQPGG
EIVLTQSPGTL
N/A
N/A






SLRLSCAASGFTFSSY
SLSPGERATLS








WMSWVRQAPGKGLEWV
CRASQSVSSTY








ANINQDGSDKYYVDSV
LAWYQQKPGQA








KGRFTISRDNVKNSLY
PRLLIFGASSR








LQINSLRAEDTAVYYC
ATGIPDRFSGS








AREGGQWLTLDYWGQG
GSGTDFTLTIS








TLVTVSS
RLEPEDFAVYY









CQQYGSSPFTF









GPGTKVDIK








3567
3568
3569
3570





42
75110_06C16A
IgG1
Kappa
QVQLQESGPGLVTPSE
DIQMTQSPSSL
N/A
N/A






TLSLSCTVSGGSISDY
SASVGDRVTIT








YWSWIRQPGGKGLEWI
CQASHDISNYL








GRIYSSGSTNYNPSLK
NWYQQKPGKAP








SRVTMSVDTSKNQFSL
KLLIYAASNLE








KLSSVTAADTAVYFCA
TGVPSRFSGSG








RDREDYYYYGMDVWGQ
SGTDFSFTISS








GTTVTVSS
LQPEDIATYYC









QQYDHLPLTFG









GGTKVEIK








3601
3602
3603
3604





43
75110_06D16A
IgG1
Kappa
QVQLQQWGAGLLKPSE
DIQMTQSPSSV
N/A
N/A






TLSLTCAVYGGSFSGY
SASVGDRVTIT








YWSWIRQPPGKGLEWI
CRASQDIADWL








GEINHSGSTNYNPSLK
AWYQQKPGKAP








SRVTISVVTSKNQFSL
KLLIYAASSFQ








KLSSVTAADTAVYYCA
SGVPSRFSGSG








RVLNWFDPWGQGTLVT
SGTDFTLTISS








VSS
LQPEDFATYFC









QQANSFPYTFG









QGTKLEIK








3635
3636
3637
3638





44
75110_06E14A
IgG1
Kappa
QVQLQESGPGLVKPSE
DIQMTQSPSSL
N/A
N/A






TLSLTCTVSGGSISNY
SASVGDRVTIT








FWSWIRQPAGKGLEWI
CQASQDISNYL








GRIYSSGNTNYNPSLK
NWYQQKPGKAP








SRVTMSVDTSKNQFSL
KLLIYGASILE








KLSSVTAADTAVYYCA
TGVPSRFTGSG








RDREDYYYYGMDVWGQ
SGTDFTFTISS








GTTVTVSS
LQPEDIATYYC









QQYDSLPITFG









QGTRLEIK








3669
3670
3671
3672





45
75110_06G04A
IgG1
Kappa
QVQLLESGPGLVKPSE
DIQMTQSPSSL
N/A
N/A






TLSLTCTVSGGSISSY
SASVGDRVTIT








YWSWIRQPAGKGLEWI
CQASQDISNYL








GRIYISGSTNYNPSLK
NWYQQKPGKAP








SRVTMSIDTSENQFSL
KLLIYNASTLE








NLSSVTAADTAVYYCA
TGVPSRFSGSG








RELERPYYYGMDVWGQ
SGTDFTFTISS








GTTVTVSS
LQPEDIATYYC









QQYDNLPLTFG









GGTKVEFK








3703
3704
3705
3706





46
75110_06K03A
IgG1
Kappa
QVQLQESGPGLVKPSE
DIQMTQSPSSL
N/A
N/A






TLSLTCTVSGGSISTY
SASVGDRVTIT








YWSWIRQPAGKGLEWI
CQASQDISNYL








GRINTSGSTTYNPSLK
NWYQQKPGKAP








SRVTMSVDTSKNQFSL
KLLIYYASILE








KLSSVTAADTAVYYCA
TGVPSRFSGSG








RELERYYYYGMDVWGQ
SGTDFTFTISS








GTTVTVSS
LQPEDIATYYC









QQYDSLPLTFG









GGTKVEIK








3737
3738
3739
3740





47
75110_07B16A
IgG1
Kappa
QVQLQQWGAGLLKPSE
DIQMTQSPSSV
N/A
N/A






TLSLTCAVYGGSFSGY
SASVGDRVTIT








YWSWIRQSPGKGLEWI
CRASQGISSWL








GEINQSGSTNYNPSLK
AWYQQKPGKAP








SRVTISVDTSKDQFSL
KLLIYDASSFQ








KLSSVTAADTAVYYCA
SGVPSRFSGSG








RVINWFDSWGQGSLVT
SGTDFTLTISS








VSS
LQTDDFATYYC









QQANSFPYTFG









QGTKLEIK








3771
3772
3773
3774





48
75110_07E04A
IgG1
Kappa
EVQLVESGGGLVQPGG
EIVLTQSPGTL
N/A
N/A






SLRLSCAVSGFTFSSY
SLSPGERATLS








DMHWVRQATGKGLEWV
CRASQSISSTY








STIGTAGDTYYPGSVK
LAWYQQKPGQA








GRFTISRENAKKFLYL
PRLLIYGASSR








QMNSLRAGDTAVYYCA
ATGIPDRFSGS








RGGYYYYGMDVWGQGT
GSGTDFTLTIS








TVTVSS
RLEPEDFAVYY









CQQYGSSPFTF









GPGTKVDIK








3805
3806
3807
3808





49
75110_07H07A
IgG1
Kappa
EVQVVESGGGLVQPGG
DIQMTQSPSSV
N/A
N/A






SLRLSCAASGFTFSSY
SGSVGDRVTIT








WMSWVRQAPGKGLEWV
CRASQGISSWL








ANIKEEGSEKYYVDSV
AWYQQKPGKAP








KGRFTISRDNAKNSLY
KLLIFGASSLQ








LQMNSLRAEDTAVYYC
SGVPSRFSGSG








VREGGQWLALDYWGQG
SGTDFTLTISS








TLVTVSS
LQPEDFATYYC









QQANSFPWTFG









QGTKVQIK








3839
3840
3841
3842





50
75110_07J02A
IgG1
Kappa
EVQLVESGGGLVQPGG
AIQMTQSPSSL
EVQLVESGGGLVQP
AIQMTQSPSSLSA






SLRLSCAASGFTFSSY
SASVGDRVTIT
GGSLRLSCAASGFT
SVGDRVTITCRAS






WMSWVRQAPGKGLEWV
CRASQGIRNDL
FSSYWMSWVRQAPG
QGIRNDLGWYQQK






ANIKEDGSEKYYVDSV
GWYQQKPGKAP
KGLEWVANIKEDGS
PGKAPKLLIYAAS






KGRFTISRDNAKNSLY
KLLIYAASSLQ
EKYYVDSVKGRFTI
SLQSGVPSRFSGR






LQMNSLRAEDTAVYYC
SGVPSRFSGRG
SRDNAKNSLYLQMN
GSGTDFALTISSL






ARDGSYSGYGMDVWGQ
SGTDFALTISS
SLRAEDTAVYYCAR
QPEDFATYYCLLD






GTTVTVSS
LQPEDFATYYC
DGSYSGYGMDVWGQ
YNYPYTFGQGTRL







LLDYNYPYTFG
GTTVTVSSASTKGP
EIKRTVAAPSVFI







QGTRLEIK
SVFPLAPSSKSTSG
FPPSDEQLKSGTA








GTAALGCLVKDYFP
SVVCLLNNFYPRE








EPVTVSWNSGALTS
AKVQWKVDNALQS








GVHTFPAVLQSSGL
GNSQESVTEQDSK








YSLSSVVTVPSSSL
DSTYSLSSTLTLS








GTQTYICNVNHKPS
KADYEKHKVYACE








NTKVDKKVEPKSCD
VTHQGLSSPVTKS








KTHTCPPCPAPEAA
FNRGEC








GGPSVFLFPPKPKD









TLMISRTPEVTCVV









VSVSHEDPEVKFNW









YVDGVEVHNAKTKP









REEQYNSTYRVVSV









LTVLHQDWLNGKEY









KCKVSNKALPAPIE









KTISKAKGQPREPQ









VYTLPPSRDELTKN









QVSLTCLVKGFYPS









DIAVEWESNGQPEN









NYKTTPPVLDSDGS









FFLYSKLTVDKSRW









QQGNVFSCSVMHEA









LHNHYTQKSLSLSP









GK







3873
3874
3875
3876





51
75110_07J24A
IgG1
Kappa
QAQLQESGPGLVKPSE
DIVMTQTPLSL
N/A
N/A






TLSLTCTVSGGSISSY
PVTPGEPASIS








YYNWIRQPAGKGLEWI
CRSSQSLLDSD








GRIYTSGRTDYNPSLK
DGNTYLDWYLQ








SRVTMSADTSKNQFSL
KPGQSPHLLIY








KLSSVTAADTAVYYCA
TLSYRASGVPD








RDEGPTDAFDIWGQGT
RFSGSGSGSDF








MVTVSS
TLKISRVEAED









VGVYYCMQRIE









FPFTFGPGTKV









DIK








3907
3908
3909
3910





52
75110_07N04A
IgG1
Kappa
QVQLQESGPGLVKPSE
DIQMTQSPSSL
N/A
N/A






TLSLTCSVSGVSSTSF
SASVGDRVTIT








YWSWIRQPAGKGLDWI
CQASQDISNYL








GRIYTSGSTNYNPSLK
TWYQQKPGKAP








SRVTMSVDTSKNQFSL
KLLIYDTSNLE








KLSSVTAADTAVYYCA
TGVPSRFSGSG








RDPGYSDAFAIWGQGT
SGTDFTFTISS








MVTVSS
LQPEDIATYYC









QQYDNLPLTFG









GGTKVEIK








3941
3942
3943
3944





53
75110_08A13A
IgG1
Kappa
EVQLVESGGGLVQPGG
AIQMTQSPSSL
EVQLVESGGGLVQP
AIQMTQSPSSLSA






SLRLSCAASGFIFSSY
SASVGDRVTIT
GGSLRLSCAASGFI
SVGDRVTITCRAS






WMSWVRQAPGKGLEWV
CRASQGIRDDL
FSSYWMSWVRQAPG
QGIRDDLGWYQQK






ANIKQDGSEKYYMDSV
GWYQQKPGKAP
KGLEWVANIKQDGS
PGKAPKLLIFAAS






KGRFTISRDNAKNSLY
KLLIFAASSLQ
EKYYMDSVKGRFTI
SLQSGVPSSFSGS






LQMNSLRAEDTAVYYC
SGVPSSFSGSG
SRDNAKNSLYLQMN
GSGTDFTLTISSL






ARDNSYYYYGMDVWGQ
SGTDFTLTISS
SLRAEDTAVYYCAR
QPEDFATYYCLHH






GTTVTVSS
LQPEDFATYYC
DNSYYYYGMDVWGQ
YNYPYTFGQGTKL







LHHYNYPYTFG
GTTVTVSSASTKGP
EIKRTVAAPSVFI







QGTKLEIK
SVFPLAPSSKSTSG
FPPSDEQLKSGTA








GTAALGCLVKDYFP
SVVCLLNNFYPRE








EPVTVSWNSGALTS
AKVQWKVDNALQS








GVHTFPAVLQSSGL
GNSQESVTEQDSK








YSLSSVVTVPSSSL
DSTYSLSSTLTLS








GTQTYICNVNHKPS
KADYEKHKVYACE








NTKVDKKVEPKSCD
VTHQGLSSPVTKS








KTHTCPPCPAPEAA
FNRGEC








GGPSVFLFPPKPKD









TLMISRTPEVTCVV









VSVSHEDPEVKFNW









YVDGVEVHNAKTKP









REEQYNSTYRVVSV









LTVLHQDWLNGKEY









KCKVSNKALPAPIE









KTISKAKGQPREPQ









VYTLPPSRDELTKN









QVSLTCLVKGFYPS









DIAVEWESNGQPEN









NYKTTPPVLDSDGS









FFLYSKLTVDKSRW









QQGNVFSCSVMHEA









LHNHYTQKSLSLSP









GK







3975
3976
3977
3978





54
75110_08D24A
IgG1
Kappa
QVQLQESGPGLVKPSE
DIQMTQSPSSL
N/A
N/A






TLSLTCTVSGGSISGF
SASVGDRVTIT








YWSWIRQPAGKGLEWI
CQASQDISNYL








GRIYTSENTNYNPSLK
NWYQQKPGKAP








SRVTMSVDTSKNQFSL
KLLIYAASNLE








KLSSVTAADTAVYYCA
TGVPSRFSGSG








RDREGYYYYGMDVWGQ
SGTDFTFTISS








GTTVTVSS
LQPEDIATYYC









QQYDSLPITFG









QGTRLEIK








4009
4010
4011
4012





55
75110_08F20A
IgG1
Kappa
QVQLQESGPGLVKPSE
DIQMTQSPSSL
N/A
N/A






TLSLTCSVSGGSISTY
SASVGDRVTIT








YWSWIRQPAGKGLEWI
CQASQDISKYL








GRICTTENTNYNPSLK
NWYQQKPGIAP








SRVTMSIDSSKNQFSL
KLLIYDASNLE








KLSSVTAADTAVYYCA
TGVPSRFSGSG








RDLERLNYYGMDVWGQ
SGTDFTFTISS








GATVTVSS
LQPEDFATYYC









QQYDSLPITFG









QGTRLEIK








4043
4044
4045
4046





56
75110_08G08A
IgG1
Kappa
QVQLQESGPGLVKPSE
DIQMTQSPSSL
N/A
N/A






TLSLTCSVSGGSISTY
SASVGDRVTIT








YWSWIRQPAGKGLEWI
CQASQDISNYL








GRICTTENTNYNPSLK
NWYQQKPGIAP








SRVTMSIDSSKNQFSL
KLLIYDASNLE








KLSSVTAADTAVYYCA
TGVPSRFSGSG








RDLERLNYYGMDVWGQ
SGTDFTFTISS








GATVTVSS
LQPEDIATYYC









QQYDSLPITFG









QGTRLEIK








4077
4078
4079
4080





57
75110_08H06A
IgG1
Kappa
EVQLVESGGGLVQPGG
EIVLTQSPGTL
N/A
N/A






SLRLSCAASGFTFSNY
SLSPGERATLS








DMHWVRQATGKGLEWV
CRASQSITSIY








STIGTAGDTYYPGSVK
LAWYRQKPGQA








GRFTISRENAKNSLYL
PRLLIYGASSR








QMNSLRAGDTAVYYCA
ATGIPDRFSGS








RGGYDYYGMDVWGQGT
GSGTDFTLTIS








TVTVSS
RLEPEDFAVYY









CQQYGSSPFTF









GPGTKVDIK








4111
4112
4113
4114





58
75110_08H11A
IgG1
Kappa
EVQLVESGGGLVQPGG
EIVLTQSPGTL
N/A
N/A






SLRLSCAASGFTFSSY
SLSPGERATLS








DMHWVRQATGKGLEWV
CGASQSVSSTY








STIGTAGDTYYPGSVK
LAWYQQKPGQA








GRFTISRENAKNSLYL
PRLLIYGASSR








QMNSLRAGDTAVYYCA
ATGIPDRFSGS








RGGYSYYGMDVWGQGT
GSGTDFTLTIS








TVTVSS
RLEPEDFAVYY









CQQFGSSPFTF









GPGTKVDIK








4145
4146
4147
4148





59
75110_08K12A
IgG1
Kappa
EVQLVESGGGLVQPGG
EIVLTQSPGTL
EVQLVESGGGLVQP
EIVLTQSPGTLSL






SLRLSCAASGFTFSSY
SLSPGERATLS
GGSLRLSCAASGFT
SPGERATLSCRAS






DMHWVRQATGKGLEWV
CRASQSVSSTY
FSSYDMHWVRQATG
QSVSSTYLAWYQQ






STIGTAGDTYYPGSVK
LAWYQQKPGQA
KGLEWVSTIGTAGD
KPGQAPRLLIYGA






GRFTISRENAENSLYL
PRLLIYGASNR
TYYPGSVKGRFTIS
SNRATGIPDRFSG






QMNSLRAGDTALYYCA
ATGIPDRFSGS
RENAENSLYLQMNS
SGSGTDFTLTISR






RGDYYYYGMDVWGQGT
GSGTDFTLTIS
LRAGDTALYYCARG
LEPEDFAVYYCQQ






TVTVSS
RLEPEDFAVYY
DYYYYGMDVWGQGT
FGTSPFTFGPGTK







CQQFGTSPFTF
TVTVSSASTKGPSV
VDIKRTVAAPSVF







GPGTKVDIK
FPLAPSSKSTSGGT
IFPPSDEQLKSGT








AALGCLVKDYFPEP
ASVVCLLNNFYPR








VTVSWNSGALTSGV
EAKVQWKVDNALQ








HTFPAVLQSSGLYS
SGNSQESVTEQDS








LSSVVTVPSSSLGT
KDSTYSLSSTLTL








QTYICNVNHKPSNT
SKADYEKHKVYAC








KVDKKVEPKSCDKT
EVTHQGLSSPVTK








HTCPPCPAPEAAGG









PSVFLFPPKPKDTL









MISRTPEVTCVVVS









VSHEDPEVKFNWYV









DGVEVHNAKTKPRE









EQYNSTYRVVSVLT









VLHQDWLNGKEYKC









KVSNKALPAPIEKT









ISKAKGQPREPQVY









TLPPSRDELTKNQV









SLTCLVKGFYPSDI









AVEWESNGQPENNY









KTTPPVLDSDGSFF









LYSKLTVDKSRWQQ









GNVFSCSVMHEALH









NHYTQKSLSLSPGK









SFNRGEC







4179
4180
4181
4182





60
75110_08M20A
IgG1
Kappa
QVQLQESDPGLVKPSE
DIQMTQSPSSL
QVQLQESDPGLVKP
DIQMTQSPSSLSA






TLSLTCTVSGGSISSY
SASVGDRVTIT
SETLSLTCTVSGGS
SVGDRVTITCQAS






YWSWIRQPAGKGLEWI
CQASQDISKYL
ISSYYWSWIRQPAG
QDISKYLNWYQQK






GRIYASGSTNYNPSLK
NWYQQKPGKAP
KGLEWIGRIYASGS
PGKAPNLLIYAAS






SRVTMSVDTSKNQFSL
NLLIYAASNLE
TNYNPSLKSRVTMS
NLETGVPSRFSGS






KLSSVTAADTAVYYCA
TGVPSRFSGSG
VDTSKNQFSLKLSS
GSGTDFTFTISSL






RDREGYYYYGMDVWGQ
SGTDFTFTISS
VTAADTAVYYCARD
QPEDIAAYYCQQY






GTTVTVSS
LQPEDIAAYYC
REGYYYYGMDVWGQ
DSLPITFGQGTRL







QQYDSLPITFG
GTTVTVSSASTKGP
EIKRTVAAPSVFI







QGTRLEIK
SVFPLAPSSKSTSG
FPPSDEQLKSGTA








GTAALGCLVKDYFP
SVVCLLNNFYPRE








EPVTVSWNSGALTS
AKVQWKVDNALQS








GVHTFPAVLQSSGL
GNSQESVTEQDSK








YSLSSVVTVPSSSL
DSTYSLSSTLTLS








GTQTYICNVNHKPS
KADYEKHKVYACE








NTKVDKKVEPKSCD
VTHQGLSSPVTKS








KTHTCPPCPAPEAA
FNRGEC








GGPSVFLFPPKPKD









TLMISRTPEVTCVV









VSVSHEDPEVKFNW









YVDGVEVHNAKTKP









REEQYNSTYRVVSV









LTVLHQDWLNGKEY









KCKVSNKALPAPIE









KTISKAKGQPREPQ









VYTLPPSRDELTKN









QVSLTCLVKGFYPS









DIAVEWESNGQPEN









NYKTTPPVLDSDGS









FFLYSKLTVDKSRW









QQGNVFSCSVMHEA









LHNHYTQKSLSLSP









GK







4213
4214
4215
4216





61
75110_09G15A
IgG1
Kappa
EVQLVESGGGLVQPGG
DIQMTQSPSSV
N/A
N/A






SLRLSCAASGFTFSDY
SASVGDRVTIT








WMSWVRQAPGKGLEWV
CRASQGISSWL








ANINQDGSEKYSVDSV
AWYQQKPGKAP








KGRFTISRDNAKNSLY
KLLIYGASSLQ








LQMNSLRAEDTAIFYC
SGVPSRFSGSG








AREGGQWLALDYWGQG
SGTDFTLTINS








TLVTVSS
LQPEDFTTYYC









QQANIFPWTFG









QGTKVEIK








4247
4248
4249
4250





62
75110_09N20A
IgG1
Kappa
EVQLVESGGGLVQPGG
DIQMTQSPSSV
EVQLVESGGGLVQP
DIQMTQSPSSVSA






SLRLSCAASGFTFSSY
SASVGDRVTIT
GGSLRLSCAASGFT
SVGDRVTITCRAS






WMSWVRQAPGKGLEWV
CRASQGISSWL
FSSYWMSWVRQAPG
QGISSWLAWYQQK






ANINEDGSEKYYVDSV
AWYQQKPGKAP
KGLEWVANINEDGS
PGKAPKLLIYAAS






KGRFTISRDNAKNSLY
KLLIYAASSLQ
EKYYVDSVKGRFTI
SLQSGVPSSFSGS






LQMNSLRAEDTAVYYC
SGVPSSFSGSG
SRDNAKNSLYLQMN
GSGTDFTLTINSL






VREGGQWLALDYWGQG
SGTDFTLTINS
SLRAEDTAVYYCVR
QPEDFATYYCQQA






TLVTVSS
LQPEDFATYYC
EGGQWLALDYWGQG
NSFPWTFGQGTKV







QQANSFPWTFG
TLVTVSSASTKGPS
AIKRTVAAPSVFI







QGTKVAIK
VFPLAPSSKSTSGG
FPPSDEQLKSGTA








TAALGCLVKDYFPE
SVVCLLNNFYPRE








PVTVSWNSGALTSG
AKVQWKVDNALQS








VHTFPAVLQSSGLY
GNSQESVTEQDSK








SLSSVVTVPSSSLG
DSTYSLSSTLTLS








TQTYICNVNHKPSN
KADYEKHKVYACE








TKVDKKVEPKSCDK
VTHQGLSSPVTKS








THTCPPCPAPEAAG
FNRGEC








GPSVFLFPPKPKDT









LMISRTPEVTCVVV









SVSHEDPEVKFNWY









VDGVEVHNAKTKPR









EEQYNSTYRVVSVL









TVLHQDWLNGKEYK









CKVSNKALPAPIEK









TISKAKGQPREPQV









YTLPPSRDELTKNQ









VSLTCLVKGFYPSD









IAVEWESNGQPENN









YKTTPPVLDSDGSF









FLYSKLTVDKSRWQ









QGNVFSCSVMHEAL









HNHYTQKSLSLSPG









K







4281
4282
4283
4284





63
75110_10K21A
IgG1
Kappa
EVQLVESGGGLVQPGG
AIQMTQSPSSL
EVQLVESGGGLVQP
AIQMTQSPSSLSA






SLRLSCAASGFTFSSY
SASVGDRVTIT
GGSLRLSCAASGFT
SVGDRVTITCRAS






WMTWVRQAPGKGLEWV
CRASQGIRNDL
FSSYWMTWVRQAPG
QGIRNDLNWYQQK






ANIKQDGSEKYYVDSV
NWYQQKPGKAP
KGLEWVANIKQDGS
PGKAPKLLIYAAS






KGRFTISRDNAKNSLY
KLLIYAASSLQ
EKYYVDSVKGRFTI
SLQSGVPSRFSGS






LQMNSLRAEDTAVYYC
SGVPSRFSGSG
SRDNAKNSLYLQMN
GSGTDFTLTISSL






VRDRYDALDIWGQGTM
SGTDFTLTISS
SLRAEDTAVYYCVR
QAEDFATYYCLKD






VTVSS
LQAEDFATYYC
DRYDALDIWGQGTM
YNYPYTFGQGTKL







LKDYNYPYTFG
VTVSSASTKGPSVF
EIKRTVAAPSVFI







QGTKLEIK
PLAPSSKSTSGGTA
FPPSDEQLKSGTA








ALGCLVKDYFPEPV
SVVCLLNNFYPRE








TVSWNSGALTSGVH
AKVQWKVDNALQS








TFPAVLQSSGLYSL
GNSQESVTEQDSK








SSVVTVPSSSLGTQ
DSTYSLSSTLTLS








TYICNVNHKPSNTK
KADYEKHKVYACE








VDKKVEPKSCDKTH
VTHQGLSSPVTKS








TCPPCPAPEAAGGP
FNRGEC








SVFLFPPKPKDTLM









ISRTPEVTCVVVSV









SHEDPEVKFNWYVD









GVEVHNAKTKPREE









QYNSTYRVVSVLTV









LHQDWLNGKEYKCK









VSNKALPAPIEKTI









SKAKGQPREPQVYT









LPPSRDELTKNQVS









LTCLVKGFYPSDIA









VEWESNGQPENNYK









TTPPVLDSDGSFFL









YSKLTVDKSRWQQG









NVFSCSVMHEALHN









HYTQKSLSLSPGK







4315
4316
4317
4318





64
75110_10L22A
IgG1
Kappa
EVQLVESGGGLVQPGG
EIVLTQSPGTL
N/A
N/A






SLRLSCAASGFTFSSY
SLSPGERATLS








DMHWVRQATGKGLEWV
CRASQSVSSSY








STIGTAGDTYYPGSVK
LAWYQQKPGQA








GRFTISRENAKNSLYL
PRLLIYGASSR








QMNGLRAGDTAVYYCA
ATGIPDRFSGS








RGNYFYYGVDVWGQGT
GSGTDFTLTIS








TVTVSS
RLEPEDFAVYY









CQQYGISPFTF









GPGTKVDIK








4349
4350
4351
4352





65
75110_10N21A
IgG1
Kappa
EVQLVESGGGLVQPGG
EIVLTQSPGTL
N/A
N/A






SLRLSCAASGFTFSSY
SLSPGERATLS








DMHWVRQVTGKGLEWV
CRASQSFISSY








STIGTAGDTYYPGSVK
LAWYQQKPGQA








GRFTISRENAKNSLYL
PRLLIYGASSR








QMNSLRAGDTAVYYCA
ATGIPDRFSGS








RGGYYYYGMDVWGQGT
GSGTDFTLTIS








TVTVSS
RLDPEDFAVYY









CQQSGNSPFTF









GPGTKVDVK








4383
4384
4385
4386





66
75110_10O16A
IgG1
Kappa
EVQLVESGGGLVQPGG
ENVLTQSPGTL
N/A
N/A






SLRLSCAASGFTFSNS
SLSPGERATLS








DMHWVRQATGKGLEWV
CRASQSVSSSY








STIGTAGDTYYPGSVK
LAWYQQKPGQA








GRFTISRENAKNSLYL
PRLLIYGASSR








QMNSLRAGDTAVYYCA
ATGIPDRFSGS








RGGLYYYGMDVWGQGT
GSGTDFTLTIS








TVTVSS
RLEPEDFAVYY









CHQFGSSPFTF









GPGTKVDIK








4417
4418
4419
4420





67
75110_11D03A
IgG1
Kappa
EVQLVESGGGLVQPGG
DIQMTQSPSSV
N/A
N/A






SLRLSCAASGFTFSSY
SASVGDRVTIT








WMSWVRQAPGKGLEWV
CRASQGISSWL








ANINQDGNEKYYVDSV
AWYQQKPGKAP








KGRFTISRDNAKNSLF
KFLISGASSLQ








LQMNSLRAEDTAVYYC
SGVPSRFSGSG








AREGGQWLALDYWGQG
SGTDFTLTISS








ALVTVSS
LQPEDFATYYC









QQANSFPWTFG









QGTKVEIK








4451
4452
4453
4454





68
75110_12C19A
IgG1
Kappa
EVQLVESGGGLVQPGG
DIQMTQSPSSV
N/A
N/A






SLRLSCAASGFTFSSY
SGSVGDRVTIT








WMSWVRQAPGKGLEWV
CRASQGISSWL








ANIKEDGSDKYYVDSV
AWYQQKPGKAP








KGRFTISRDNAKNSLY
KLLIYGASSLQ








LQMNSLRAEDTAVHYC
SGVPSRFSGSG








VREGGQWLALDYWGQG
SGTDFTLTISS








TLVTVSS
LQPEDFVTYYC









QQANSFPWTFG









QGTKVEIK








4485
4486
4487
4488





69
75110_12H17A
IgG1
Kappa
EVQLVESGGGLVQPGG
DIQMTQSPSSV
N/A
N/A






SLRLSCAASGFTFSDY
SASVGDRVTIT








WMSWVRQAPGKGLEWV
CRASQGISSWL








ANIKEDGNEKYYVDSV
AWYQQKPGKAP








KGRFTISRDNAKNSLF
KFLISGASSLQ








LQMNSLRAEDTAVYYC
SGVPSRFTGSG








AREGGQWLALDYWGQG
SGTDFTLTISS








ALVTVSS
LQPEDFATYYC









QQANSFPWTFG









QGTKVEIK








4519
4520
4521
4522





70
75110_12H19A
IgG1
Kappa
EVQLVESGGGLVQPGG
DIQMTQSPSSV
N/A
N/A






SLRLSCAASGFTFSSY
SASVGDRVSIT








WMSWVRQAPGQGLEWV
CRASQGISSWL








ANINEDGNEKYHVDSV
AWYQQKPGKAP








KGRLTISRDNAKNSLY
KLLIYGASGLQ








LQMNSLRGVDTAVYFC
SGVPSRFSGSG








AREGGQWLALDYWGQG
SGTDFTLTISS








ALVTVSS
LQPEDFATYYC









QQANSFPWTFG









QGTKVEIK








4553
4554
4555
4556





71
75110_12K21A
IgG1
Kappa
QVQLQQWGAGLLKPSE
DIQMTQSPSSV
QVQLQQWGAGLLKP
DIQMTQSPSSVSA






TLSLTCAVSGGSFSGY
SASVGDRVTIT
SETLSLTCAVSGGS
SVGDRVTITCRAS






YWSWIRQPPGKGLEWI
CRASPDIANWL
FSGYYWSWIRQPPG
PDIANWLAWYQQK






GEINHSGSTNCNPSLK
AWYQQKPGKAP
KGLEWIGEINHSGS
PGKAPELLIYAAS






SRVTISVDTSNNQFSL
ELLIYAASSLQ
TNCNPSLKSRVTIS
SLQSGVPSRFSGS






KLSSVTAADTAVYYCA
SGVPSRFSGSG
VDTSNNQFSLKLSS
GSGTDFTLTISSL






RVLNYFDYWGQGTLVT
SGTDFTLTISS
VTAADTAVYYCARV
QPEDFATYFCQQA






VSS
LQPEDFATYFC
LNYFDYWGQGTLVT
NSFPLTFGGGTKV







QQANSFPLTFG
VSSASTKGPSVFPL
ESKRTVAAPSVFI







GGTKVESK
APSSKSTSGGTAAL
FPPSDEQLKSGTA








GCLVKDYFPEPVTV
SVVCLLNNFYPRE








SWNSGALTSGVHTF
AKVQWKVDNALQS








PAVLQSSGLYSLSS
GNSQESVTEQDSK








VVTVPSSSLGTQTY
DSTYSLSSTLTLS








ICNVNHKPSNTKVD
KADYEKHKVYACE








KKVEPKSCDKTHTC
VTHQGLSSPVTKS








PPCPAPEAAGGPSV
FNRGEC








FLFPPKPKDTLMIS









RTPEVTCVVVSVSH









EDPEVKFNWYVDGV









EVHNAKTKPREEQY









NSTYRVVSVLTVLH









QDWLNGKEYKCKVS









NKALPAPIEKTISK









AKGQPREPQVYTLP









PSRDELTKNQVSLT









CLVKGFYPSDIAVE









WESNGQPENNYKTT









PPVLDSDGSFFLYS









KLTVDKSRWQQGNV









FSCSVMHEALHNHY









TQKSLSLSPGK







4587
4588
4589
4590





72
75110_13C07A
IgG1
Kappa
EVQLVESGGVLVQPGG
EIVLTQSPGTL
N/A
N/A






SLRLSCAASGFTFSNY
SLSPGERATLS








DMHWVRQATGKGLEWV
CRASQSVSSSY








STIGTAGDTYYPGSVK
LAWYQQKPGQA








GRFTLSRENAKNSLYL
PRLLIYGASSR








QMHSLRAGDTAVYYCA
ATGIPDRFSGS








RGAYGYYGMDVWGQGT
GSGTDFILTIS








TVTVSS
RLEPEDFAVYY









CQQYGFSPFTF









GPGTKVDIK








4621
4622
4623
4624





73
75110_13C13A
IgG1
Kappa
QVQLQQWGAGLLKPSE
DIQMTQTPSSV
N/A
N/A






TLSLTCAVSGGSFSGY
SASVGDRVTIT








YWSWIRQPPGKGLEWI
CRASPGISNWL








GEINHSGSTNCNPSLK
AWYQQKPGKAP








SRVTISVDTSKNQFSL
ELLIYAASSLQ








KLSSVTAADTAMYYCA
SGVPSRFSGSG








RVLNFFDYWGQGTLVT
SGTDFTLTISS








VSS
LQPEDFATYFC









QQANSFPLTFG









GGTKVESK








4655
4656
4657
4658





74
75110_13P21A
IgG1
Kappa
QVQLQQWGAGLLKPSE
DIQMTQSPSSV
N/A
N/A






TLSLTCAVSGGSFSGY
SASVGDRVTIT








YWSWIRQPPGKGLEWI
CRASPDIANWL








GEINHSGSTNCNPSLK
AWYQQKPGKAP








SRVTISVDTSNNQFSL
ELLIYAASSLQ








KLSSVTAADTAVYYCA
SGVPSRFSGSG








RVLNYFDYWGQGTLVT
SGTDFTLTISS








VSS
LQPEDFATYFC









QQANSFPLTFG









GGTKVESK








4689
4690
4691
4692





75
75110_13P22A
IgG1
Kappa
QVQLQQWGAGLLKPSE
DIQMTQSPSSV
N/A
N/A






TLSLTCAAYGGSFSGY
SASVGDRVTIT








YWSWIRQSPGKGLEWI
CRASQGISDWL








GEINQSGNTNYNPSLK
AWYQQKSGKAP








SRVTISADTSKNQFSL
DLLIFAASSLQ








KLSSVTAADTAVYYCA
SGVPSRFSGSG








RVLNWFDYWGQGILVT
SGTDFTLTISS








VSS
LQPEDFATYYC









QQANSFPYTFG









QGTKLEIK








4723
4724
4725
4726





76
75110_14G10A
IgG1
Kappa
EVQLVESGGGLVKPGG
DIQMTQSPSSL
N/A
N/A






SLRLSCAASGFTFSSY
SASVGDRVTIT








SMNWVRQAPGKGLEWV
CQASQDISNYL








SFISSSSSYIYYADSV
NWYQQKPGKAP








KGRFTISRDNAKNSLY
KLLIYDASNLE








LQMNSLRAEDTAVYYC
TGVPSRFSGSG








ARERGDDYGDYEGAFD
SGTDFTFTISS








IWGQGTMVTVSS
LQPEDIATYYC









QQYDNLPYTFG









QGTKLEIK








4757
4758
4759
4760





77
75110_14H13A
IgG1
Kappa
EVQLVESGGGLVQPGG
EIVLTQSPGTL
N/A
N/A






SLRLSCAASGFTFSNY
SLSPGERATLS








DMHWVRQATGKGLEWV
CRASQSVSSSY








STIGTAGDTYYPGSVK
LAWYQQKPGQA








GRFTISRKNAKNSLYL
PRLLIYGASSR








QMISLRAGDTAVYYCA
ATGIPDRFSGS








RGGDYYYGMDVWGQGT
GSGTDFTLTIS








TVTVSS
RLEPEDFAVYY









CQQFGSSPFTF









GPGTKVDIK








4791
4792
4793
4794





78
75110_14I16A
IgG1
Kappa
QVQLQESGPGLVKPSE
DIQMTQSPSSL
N/A
N/A






TLSLTCTVSNGSISSY
SASVGDRVTIT








YWSWIRQSAGKGLEWI
CQASHDISNYL








GRIYTSGSTNYNPSLK
NWYQQKPGKAP








SRVTMLVDTSKNQFSL
KLLLYYASNLE








KLSSVTAADTAVYYCA
TGVPSRFSGSG








RDREDYYYYGMDVWGQ
SGTDFTFTITS








GTTVTVSS
LQPEDIGTYSC









QQYDNLPLTFG









GGTKVEIK








4825
4826
4827
4828





79
75110_14N19A
IgG1
Kappa
QVQLQESGPGLVKPSE
DIQMTQFPSSL
N/A
N/A






TLSLTCTVSGGSISRY
SASVGDRVTIT








YWSWIRQPAGKGLEWI
CQASQDISNYL








GRICTSENPNYNPALK
NWYQQKPGKAP








SRVTMSVDTSKNQFSL
KLLIYDASNLE








KLSSVTAADTAVYYCA
SGVPSRFSGRG








RELERLNYYGMDVWGQ
SGTDFTFTISS








GTTVTVSS
LQPEDFATFYC









QQYDTLPITFG









QGTRLEIK








4859
4860
4861
4862





80
75110_14P05A
IgG1
Kappa
EVQLVESGGGLVQPGG
EIVLTQSPGTL
N/A
N/A






SLRLSCAASGFTFSSY
SLSPGERATLS








DVHWVRQATGKGLEWV
CRASQSVSSSY








STIGTAGDTYYPGSVK
LAWYQQKPGQT








GRFTISRENAKNSLYL
PRLLIYGASSR








QMNSLRAGDTAVYYCA
ATGIPDRFSGS








RGGFYYYGMDVWGQGT
GSGTDFTLTIS








TVTVSS
RLEPEDFAVFY









CQQSGSSPFTF









GPGTKVDVK








4893
4894
4895
4896





81
75110_14P08A
IgG1
Kappa
QVQLQESGPGLVKSSE
DIVMTQTPLSL
N/A
N/A






TLSLTCTDSGDSIRSY
PVTPGEPASIS








YWNWIRQPAGKGLEWI
CRSSQSLLDSD








GRIYASGSTNYNPSLK
DGNTYLDWYLQ








SRVIMSADTSKNRFSL
KPGQSPQLLIY








KLSSVTAADTAVYYCA
TLSYRASGVPD








RDGGVGDSLDYWGQGT
RFSGSGSGTDF








LVTVSS
TLKISRVEAED









VGVYYCMQRIE









FPFTFGPGTKV









DIK








4927
4928
4929
4930





82
75110_01A07A_2
IgG1
Kappa
QVQLQESGPGLVKPSE
DIQMTQSPSAM
N/A
N/A






TLSLTCTVSGGSIINY
SASVGDRVTIT








YWSWIRQPAGKGLEWI
CRASQGITNYL








GRIYSSGSTNYKSSLK
AWFQQKPGKVP








SRVTMSVDTSKNQFYL
KRLIYVTSSFQ








KLRSVTAADTAVYYCA
SGVPSRFSASG








REREAYLYYGLDVWGQ
SGTEFNLTISG








GTTVTVSS
LQPEDFAIYYC









LQHNNYPLTFG









GGTKVEIK








4961
4962
4963
4964
















TABLE 12







Kabat CDR Amino Acid Sequences of CD4 Antibodies
















HC









Kabat

HC Kabat
LC Kabat
LC Kabat
LC Kabat


#
Protein Name
CDR1
HC Kabat CDR2
CDR3
CDR1
CDR2
CDR3

















1
75110_01A06A
SYWMS
NINEDGNEKYYVDSVKG
EGGQWLSLDY
RASQGISSWLA
GASSLQS
QQANSFPWT




2177
2178
2179
2180
2181
2182





2
75110_01A07A_1
NYYWS
RIYSSGSTNYKSSLKS
EREAYLYYGLDV
QASQDIGNYLN
DASNLET
QQYDSLPLT




2211
2212
2213
2214
2215
2216





3
75110_01C18A
SNYMN
VIYAGDNTYSADSVKG
EGGTTGAFDI
RASQGINSWLA
AASSLQS
QQGNSFPYT




2245
2246
2247
2248
2249
2250





4
75110_01D24A
GYYWS
EINHSGSTNYNPSLKS
LVNWFDP
RASQDISNWLA
AASSLQT
QQANSFPYS




2279
2280
2281
2282
2283
2284





5
75110_01E08A
NYDMH
TIGTAGDTYYPASVKG
GGDYYYGMDV
RASQSVSSSYLA
GASSRAT
QQFGSSPFT




2313
2314
2315
2316
2317
2318





6
75110_01G11A
SYDMH
TIGTAGDTYYPGSVKG
GGDYYYGMDV
RASQNTYSSYLA
GASNRAT
QQHGTSPFT




2347
2348
2349
2350
2351
2352





7
75110_01H18A
GYYWS
EINQSGSTNYNPSLKS
VINWFDS
RASQGISSWLA
AASSFQS
QQANSFPYT




2381
2382
2383
2384
2385
2386





8
75110_01J09A
SYWMS
NTKEDGSDKYYVDSVKG
EGGQWLALDY
RASQGISSWLA
GASSLQS
QQANSFPWT




2415
2416
2417
2418
2419
2420





9
75110_01J17A
SYDMH
TIGTADDTYYPGSVKG
GGDYYYGMDV
RASQSVYISYLA
GASSRAT
QQFGSSPFT




2449
2450
2451
2452
2453
2454





10
75110_01K10A
NYDMH
TIGTAGDTYYPGSVKG
GGDYYYGMDV
RASQSLSSVYLA
GASSRAT
QQYGSSPFT




2483
2484
2485
2486
2487
2488





11
75110_01L08A
HYYWS
YIHYSGTTNYNPSLKS
DQGFSSGGMDV
QASQDISNYLN
DASNLET
QQYDNLPLT




2517
2518
2519
2520
2521
2522





12
75110_01N04A
NYDMH
TIGTAGDTYYPGSVKG
GGDFYYGLDV
RASQSVSSVYLA
GASSRAT
QQYGSSPFT




2551
2552
2553
2554
2555
2556





13
75110_02E08A
TYYWT
RVYTSGDTNYNPSLKS
DSGALYSWNYG
RASQDISNYLA
AASSLQS
LQHNSYPRT






DAFDI







2585
2586
2587
2588
2589
2590





14
75110_02E22A
SFYWS
RIYTSGSTNYNPSLKS
ELEKRNYYGMDV
QASHDISNYLN
DASTLET
QQYDSLPLT




2619
2620
2621
2622
2623
2624





15
75110_02116A
GYYWT
EINHSGTTNSNPSLKS
ELNWFDP
RASQDIANWLA
AASSLLG
QQANSFPYT




2653
2654
2655
2656
2657
2658





16
75110 02118A
SYDMH
TIGTAGDTYYPGSVKG
GGYYYYGMDV
RASQSVSSSYLA
GASSRAT
QQYGSSPFT




2687
2688
2689
2690
2691
2692





17
75110_02K11A
SGFYYWT
YISYSGNTYYNPSFKS
DRPSNFDAFDI
RASQSVSTSYLA
GASSRAT
QQYGRSPLT




2721
2722
2723
2724
2725
2726





18
75110_02N15A
SYWMS
NINEDGNEKYYVDSVKG
EGGQWLALDH
RASQGISSWLA
GASSLQS
QQANSFPWT




2755
2756
2757
2758
2759
2760





19
75110_03B16A
SYWMS
NINEDGSEKNYVDSVKG
EGGQWLALDY
RASQGIRSWLA
GASSLQS
QQANSFPWT




2789
2790
2791
2792
2793
2794





20
75110_03C01A
GYYWS
EINQSGSTNYNPSLKS
VINWFDS
RASQGISSWLA
DASSFQS
QQANSFPYT




2823
2824
2825
2826
2827
2828





21
75110_03D16A
SYWMS
NINQDGGEKYYVDSVKG
EGGQWLALDY
RASQGISSWLT
AASSLQS
QQANSFPWT




2857
2858
2859
2860
2861
2862





22
75110_03108A
SYYWS
YIYYSGSTNYNPSLKS
EGEQWFYGLDV
RASQSVSSTYLA
GSSSRAT
QQYGNSFPIT




2891
2892
2893
2894
2895
2896





23
75110_03123A
SYYWN
RIYTSGSTNYNPSLKS
DPGYSDAFNI
QASQDISNYLN
DASNLET
QQCDNLPLT




2925
2926
2927
2928
2929
2930





24
75110_03L12A
GYYWS
EINHSGSTNYNPSLKS
LINWFDP
RASQDISNWLA
AASSLQS
QQANSFPYT




2959
2960
2961
2962
2963
2964





25
75110_04B08A
NYGIH
IIWYDGSKKYYADSVKG
EDDWNDGLAY
RASQDIRNDLG
AASNLQS
LQDSNYPRT




2993
2994
2995
2996
2997
2998





26
75110_04D20A
DYYWS
RIYTSGSTNYNPSLKS
ELERYYFYGVDV
QASQDISNYLN
AASNLET
QQYDSLPLT




3027
3028
3029
3030
3031
3032





27
75110_04F22A
SYDIH
TIGTAGDTYYPGSVKG
GGYYYYGMDV
RASQSVYSSYLA
GASSRAT
QQFGTSPFT




3061
3062
3063
3064
3065
3066





28
75110_04G02A
NAWMS
RIKSKTDGGTTDYAAPV
GGWFGELWGPFDI
KSSQSVLYSSNNK
WASARES
QQYFGSFPT





KG

NYLA






3095
3096
3097
3098
3099
3100





29
75110_04G16A
SGYYYWS
YISYSGSTYYNPSLKS
DRPSNFDAFDI
RASQSVGSTYLA
GAFSRAT
QQYGSSPLT




3129
3130
3131
3132
3133
3134





30
75110_04H17A
TYYWS
RIYTSERPNYNPSLKS
ELERPYYYGMDV
QASQDISNYLN
YASNLET
QQYDNLPLT




3163
3164
3165
3166
3167
3168





31
75110_04K10A
SYWMS
NINQDGSEKYYVDSVKG
EGGQWLSLDY
RASQGISSWLA
GVSSFQS
QQANSFPWT




3197
3198
3199
3200
3201
3202





32
75110_04P06A
NYDMH
TIGTAGDTYYPGSVKG
GGDYYYGMDV
RASQSLSSVYLA
GASSRAT
QQYGSSPFT




3231
3232
3233
3234
3235
3236





33
75110_04P08A
GYYWS
EINQSGSTNYNPSLKS
VLNWFDP
RASQDISNWLA
AASSLQS
QQANSFPYT




3265
3266
3267
3268
3269
3270





34
75110_05A11A
NTWMS
RIKSKIDGGTTDYAAPV
SGTYSSGWGLFDY
QASQDISNYLN
DTSNLEA
QQYDNLPFT





KG








3299
3300
3301
3302
3303
3304





35
75110_05B13A
GYYWT
EINHRGSTNYNPSLKS
PDSNWFDP
RASQDISNWLA
AASSLQS
QQANSFPLT




3333
3334
3335
3336
3337
3338





36
75110_05E05A
SYYWS
RIYTSGSTNYNPSLKS
DGGVGDSLDY
RSSQSLLDSDDG
TLSYRAS
MQHIEFPFT







NTYLD






3367
3368
3369
3370
3371
3372





37
75110_05E13A
NAWMS
RVESKTDGGTTDYAAPVK
GGGFGLELYGFFDY
RASQSISSWLA
KASSLES
LQYNSYYT





D








3401
3402
3403
3404
3405
3406





38
75110_05F19A
NYDVH
TIGTAGDTYYPGSVKG
GGYDYYGLDV
RASQSVSSTYLA
GASSRAT
QQYGSSPFT




3435
3436
3437
3438
3439
3440





39
75110_05G15A
SGGYFW
CIYYSGSTYYIPSLKS
DGYDYWYFDL
RASQSVSSSYLA
GASSRAT
QQYGSSPYT




S









3469
3470
3471
3472
3473
3474





40
75110_05K11A
SYDMH
TIGTAGDTYYPASVKG
GGFYYYGMDV
RASQSVSNTYLA
GASSRAT
QQHGSSPFT




3503
3504
3505
3506
3507
3508





41
75110_05L07A
SYWMS
NINQDGSDKYYVDSVKG
EGGQWLTLDY
RASQSVSSTYLA
GASSRAT
QQYGSSPFT




3537
3538
3539
3540
3541
3542





42
75110_06C16A
DYYWS
RIYSSGSTNYNPSLKS
DREDYYYYGMDV
QASHDISNYLN
AASNLET
QQYDHLPLT




3571
3572
3573
3574
3575
3576





43
75110_06D16A
GYYWS
EINHSGSTNYNPSLKS
VLNWFDP
RASQDIADWLA
AASSFQS
QQANSFPYT




3605
3606
3607
3608
3609
3610





44
75110_06E14A
NYFWS
RIYSSGNTNYNPSLKS
DREDYYYYGMDV
QASQDISNYLN
GASILET
QQYDSLPIT




3639
3640
3641
3642
3643
3644





45
75110_06G04A
SYYWS
RIYISGSTNYNPSLKS
ELERPYYYGMDV
QASQDISNYLN
NASTLET
QQYDNLPLT




3673
3674
3675
3676
3677
3678





46
75110_06K03A
TYYWS
RINTSGSTTYNPSLKS
ELERYYYYGMDV
QASQDISNYLN
YASILET
QQYDSLPLT




3707
3708
3709
3710
3711
3712





47
75110_07B16A
GYYWS
EINQSGSTNYNPSLKS
VINWFDS
RASQGISSWLA
DASSFQS
QQANSFPYT




3741
3742
3743
3744
3745
3746





48
75110_07E04A
SYDMH
TIGTAGDTYYPGSVKG
GGYYYYGMDV
RASQSISSTYLA
GASSRAT
QQYGSSPFT




3775
3776
3777
3778
3779
3780





49
75110_07H07A
SYWMS
NIKEEGSEKYYVDSVKG
EGGQWLALDY
RASQGISSWLA
GASSLQS
QQANSFPWT




3809
3810
3811
3812
3813
3814





50
75110_07102A
SYWMS
NIKEDGSEKYYVDSVKG
DGSYSGYGMDV
RASQGIRNDLG
AASSLQS
LLDYNYPYT




3843
3844
3845
3846
3847
3848





51
75110_07124A
SYYYN
RIYTSGRTDYNPSLKS
DEGPTDAFDI
RSSQSLLDSDDG
TLSYRAS
MQRIEFPFT







NTYLD






3877
3878
3879
3880
3881
3882





52
75110_07N04A
SFYWS
RIYTSGSTNYNPSLKS
DPGYSDAFAI
QASQDISNYLT
DTSNLET
QQYDNLPLT




3911
3912
3913
3914
3915
3916





53
75110_08A13A
SYWMS
NIKQDGSEKYYMDSVKG
DNSYYYYGMDV
RASQGIRDDLG
AASSLQS
LHHYNYPYT




3945
3946
3947
3948
3949
3950





54
75110_08D24A
GFYWS
RIYTSENTNYNPSLKS
DREGYYYYGMDV
QASQDISNYLN
AASNLET
QQYDSLPIT




3979
3980
3981
3982
3983
3984





55
75110_08F20A
TYYWS
RICTTENTNYNPSLKS
DLERLNYYGMDV
QASQDISKYLN
DASNLET
QQYDSLPIT




4013
4014
4015
4016
4017
4018





56
75110_08G08A
TYYWS
RICTTENTNYNPSLKS
DLERLNYYGMDV
QASQDISNYLN
DASNLET
QQYDSLPIT




4047
4048
4049
4050
4051
4052





57
75110_08H06A
NYDMH
TIGTAGDTYYPGSVKG
GGYDYYGMDV
RASQSITSIYLA
GASSRAT
QQYGSSPFT




4081
4082
4083
4084
4085
4086





58
75110_08H1lA
SYDMH
TIGTAGDTYYPGSVKG
GGYSYYGMDV
GASQSVSSTYLA
GASSRAT
QQFGSSPFT




4115
4116
4117
4118
4119
4120





59
75110_08K12A
SYDMH
TIGTAGDTYYPGSVKG
GDYYYYGMDV
RASQSVSSTYLA
GASNRAT
QQFGTSPFT




4149
4150
4151
4152
4153
4154





60
75110_08M20A
SYYWS
RIYASGSTNYNPSLKS
DREGYYYYGMDV
QASQDISKYLN
AASNLET
QQYDSLPIT




4183
4184
4185
4186
4187
4188





61
75110_09G15A
DYWMS
NINQDGSEKYSVDSVKG
EGGQWLALDY
RASQGISSWLA
GASSLQS
QQANIFPWT




4217
4218
4219
4220
4221
4222





62
75110_09N20A
SYWMS
NINEDGSEKYYVDSVKG
EGGQWLALDY
RASQGISSWLA
AASSLQS
QQANSFPWT




4251
4252
4253
4254
4255
4256





63
75110_10K21A
SYWMT
NIKQDGSEKYYVDSVKG
DRYDALDI
RASQGIRNDLN
AASSLQS
LKDYNYPYT




4285
4286
4287
4288
4289
4290





64
75110_10L22A
SYDMH
TIGTAGDTYYPGSVKG
GNYFYYGVDV
RASQSVSSSYLA
GASSRAT
QQYGISPET




4319
4320
4321
4322
4323
4324





65
75110_10N21A
SYDMH
TIGTAGDTYYPGSVKG
GGYYYYGMDV
RASQSFISSYLA
GASSRAT
QQSGNSPFT




4353
4354
4355
4356
4357
4358





66
75110_10016A
NSDMH
TIGTAGDTYYPGSVKG
GGLYYYGMDV
RASQSVSSSYLA
GASSRAT
HQFGSSPFT




4387
4388
4389
4390
4391
4392





67
75110_11D03A
SYWMS
NINQDGNEKYYVDSVKG
EGGQWLALDY
RASQGISSWLA
GASSLQS
QQANSFPWT




4421
4422
4423
4424
4425
4426





68
75110_12C19A
SYWMS
NIKEDGSDKYYVDSVKG
EGGQWLALDY
RASQGISSWLA
GASSLQS
QQANSFPWT




4455
4456
4457
4458
4459
4460





69
75110_12H17A
DYWMS
NIKEDGNEKYYVDSVKG
EGGQWLALDY
RASQGISSWLA
GASSLQS
QQANSFPWT




4489
4490
4491
4492
4493
4494





70
75110_12H19A
SYWMS
NINEDGNEKYHVDSVKG
EGGQWLALDY
RASQGISSWLA
GASGLQS
QQANSFPWT




4523
4524
4525
4526
4527
4528





71
75110_12K21A
GYYWS
EINHSGSTNCNPSLKS
VLNYFDY
RASPDIANWLA
AASSLQS
QQANSFPLT




4557
4558
4559
4560
4561
4562





72
75110_13C07A
NYDMH
TIGTAGDTYYPGSVKG
GAYGYYGMDV
RASQSVSSSYLA
GASSRAT
QQYGFSPFT




4591
4592
4593
4594
4595
4596





73
75110_13C13A
GYYWS
EINHSGSTNCNPSLKS
VLNFFDY
RASPGISNWLA
AASSLQS
QQANSFPLT




4625
4626
4627
4628
4629
4630





74
75110_13P21A
GYYWS
EINHSGSTNCNPSLKS
VLNYFDY
RASPDIANWLA
AASSLQS
QQANSFPLT




4659
4660
4661
4662
4663
4664





75
75110_13P22A
GYYWS
EINQSGNTNYNPSLKS
VLNWFDY
RASQGISDWLA
AASSLQS
QQANSFPYT




4693
4694
4695
4696
4697
4698





76
75110_14G10A
SYSMN
FISSSSSYIYYADSVKG
ERGDDYGDYEGAFDI
QASQDISNYLN
DASNLET
QQYDNLPYT




4727
4728
4729
4730
4731
4732





77
75110_14H13A
NYDMH
TIGTAGDTYYPGSVKG
GGDYYYGMDV
RASQSVSSSYLA
GASSRAT
QQFGSSPFT




4761
4762
4763
4764
4765
4766





78
75110_14116A
SYYWS
RIYTSGSTNYNPSLKS
DREDYYYYGMDV
QASHDISNYLN
YASNLET
QQYDNLPLT




4795
4796
4797
4798
4799
4800





79
75110_14N19A
RYYWS
RICTSENPNYNPALKS
ELERLNYYGMDV
QASQDISNYLN
DASNLES
QQYDTLPIT




4829
4830
4831
4832
4833
4834





80
75110_14P05A
SYDVH
TIGTAGDTYYPGSVKG
GGFYYYGMDV
RASQSVSSSYLA
GASSRAT
QQSGSSPFT




4863
4864
4865
4866
4867
4868





81
75110_14P08A
SYYWN
RIYASGSTNYNPSLKS
DGGVGDSLDY
RSSQSLLDSDDG
TLSYRAS
MQRIEFPFT







NTYLD






4897
4898
4899
4900
4901
4902





82
75110_01A07A_2
NYYWS
RIYSSGSTNYKSSLKS
EREAYLYYGLDV
RASQGITNYLA
VTSSFQS
LQHNNYPLT




4931
4932
4933
4934
4935
4936
















TABLE 13







Chothia CDR Amino Acid Sequences of CD4 Antibodies
















HC Chothia
HC Chothia
HC Chothia
LC Chothia
LC Chothia
LC Chothia


#
Protein Name
CDR1
CDR2
CDR3
CDR1
CDR2
CDR3

















1
75110_01A06A
GFTFSSY
NEDGNE
EGGQWLSLD
SQGISSW
GAS
ANSFPW




2183
2184
2185
2186
2187
2188





2
75110_01A07A_1
GGSIINY
YSSGS
EREAYLYYGLD
SQDIGNY
DAS
YDSLPL




2217
2218
2219
2220
2221
2222





3
75110_01C18A
GFTVSSN
YAGDN
EGGTTGAFD
SQGINSW
AAS
GNSFPY




2251
2252
2253
2254
2255
2256





4
75110_01D24A
GGSFSGY
NHSGS
LVNWFD
SQDISNW
AAS
ANSFPY




2285
2286
2287
2288
2289
2290





5
75110_01E08A
GFTFNNY
GTAGD
GGDYYYGMD
SQSVSSSY
GAS
FGSSPF




2319
2320
2321
2322
2323
2324





6
75110_01G11A
GFTFSSY
GTAGD
GGDYYYGMD
SQNTYSSY
GAS
HGTSPF




2353
2354
2355
2356
2357
2358





7
75110_01H18A
GGSFSGY
NQSGS
VINWFD
SQGISSW
AAS
ANSFPY




2387
2388
2389
2390
2391
2392





8
75110_01J09A
GFTFSSY
KEDGSD
EGGQWLALD
SQGISSW
GAS
ANSFPW




2421
2422
2423
2424
2425
2426





9
75110_01J17A
GFTFSSY
GTADD
GGDYYYGMD
SQSVYISY
GAS
FGSSPF




2455
2456
2457
2458
2459
2460





10
75110_01K10A
GFTFRNY
GTAGD
GGDYYYGMD
SQSLSSVY
GAS
YGSSPF




2489
2490
2491
2492
2493
2494





11
75110_01L08A
GGSISHY
HYSGT
DQGFSSGGMD
SQDISNY
DAS
YDNLPL




2523
2524
2525
2526
2527
2528





12
75110_01N04A
GFTFSNY
GTAGD
GGDFYYGLD
SQSVSSVY
GAS
YGSSPF




2557
2558
2559
2560
2561
2562





13
75110_02E08A
GGSISTY
YTSGD
DSGALYSWNYGDAFD
SQDISNY
AAS
HNSYPR




2591
2592
2593
2594
2595
2596





14
75110_02E22A
GGSISSF
YTSGS
ELEKRNYYGMD
SHDISNY
DAS
YDSLPL




2625
2626
2627
2628
2629
2630





15
75110_02116A
GGSFSGY
NHSGT
ELNWFD
SQDIANW
AAS
ANSFPY




2659
2660
2661
2662
2663
2664





16
75110_02118A
GFTFSSY
GTAGD
GGYYYYGMD
SQSVSSSY
GAS
YGSSPF




2693
2694
2695
2696
2697
2698





17
75110_02K11A
GGSISSGFY
SYSGN
DRPSNFDAFD
SQSVSTSY
GAS
YGRSPL




2727
2728
2729
2730
2731
2732





18
75110_02N15A
GFTFSSY
NEDGNE
EGGQWLALD
SQGISSW
GAS
ANSFPW




2761
2762
2763
2764
2765
2766





19
75110_03B16A
GFTFSSY
NEDGSE
EGGQWLALD
SQGIRSW
GAS
ANSFPW




2795
2796
2797
2798
2799
2800





20
75110_03C01A
GGSFSGY
NQSGS
VINWFD
SQGISSW
DAS
ANSFPY




2829
2830
2831
2832
2833
2834





21
75110_03D16A
GFTFSSY
NQDGGE
EGGQWLALD
SQGISSW
AAS
ANSFPW




2863
2864
2865
2866
2867
2868





22
75110_03108A
GGSISSY
YYSGS
EGEQWFYGLD
SQSVSSTY
GSS
YGNSFPI




2897
2898
2899
2900
2901
2902





23
75110_03123A
GGSITSY
YTSGS
DPGYSDAFN
SQDISNY
DAS
CDNLPL




2931
2932
2933
2934
2935
2936





24
75110_03L12A
GGSFSGY
NHSGS
LINWFD
SQDISNW
AAS
ANSFPY




2965
2966
2967
2968
2969
2970





25
75110_04B08A
GFNFINY
WYDGSK
EDDWNDGLA
SQDIRND
AAS
DSNYPR




2999
3000
3001
3002
3003
3004





26
75110_04D20A
NGSISDY
YTSGS
ELERYYFYGVD
SQDISNY
AAS
YDSLPL




3033
3034
3035
3036
3037
3038





27
75110_04F22A
GFTFSSY
GTAGD
GGYYYYGMD
SQSVYSSY
GAS
FGTSPF




3067
3068
3069
3070
3071
3072





28
75110_04G02A
GFTFSNA
KSKTDGGT
GGWFGELWGPFD
SQSVLYSSNNKNY
WAS
YFGSFP




3101
3102
3103
3104
3105
3106





29
75110_04G16A
GDSISSGYY
SYSGS
DRPSNFDAFD
SQSVGSTY
GAF
YGSSPL




3135
3136
3137
3138
3139
3140





30
75110_04H17A
GGSISTY
YTSER
ELERPYYYGMD
SQDISNY
YAS
YDNLPL




3169
3170
3171
3172
3173
3174





31
75110_04K10A
GFTFSSY
NQDGSE
EGGQWLSLD
SQGISSW
GVS
ANSFPW




3203
3204
3205
3206
3207
3208





32
75110_04P06A
GFTFSNY
GTAGD
GGDYYYGMD
SQSLSSVY
GAS
YGSSPF




3237
3238
3239
3240
3241
3242





33
75110_04P08A
GGSLSGY
NQSGS
VLNWFD
SQDISNW
AAS
ANSFPY




3271
3272
3273
3274
3275
3276





34
75110_05A11A
GFTFSNT
KSKIDGGT
SGTYSSGWGLFD
SQDISNY
DTS
YDNLPF




3305
3306
3307
3308
3309
3310





35
75110_05B13A
GGSFSGY
NHRGS
PDSNWFD
SQDISNW
AAS
ANSFPL




3339
3340
3341
3342
3343
3344





36
75110_05E05A
GGSIGSY
YTSGS
DGGVGDSLD
SQSLLDSDDGNTY
TLS
HIEFPF




3373
3374
3375
3376
3377
3378





37
75110_05E13A
GFSFSNA
ESKTDGGT
GGGFGLELYGFFD
SQSISSW
KAS
YNSYY




3407
3408
3409
3410
3411
3412





38
75110_05F19A
GFTFSNY
GTAGD
GGYDYYGLD
SQSVSSTY
GAS
YGSSPF




3441
3442
3443
3444
3445
3446





39
75110_05G15A
GGSISSGGY
YYSGS
DGYDYWYFD
SQSVSSSY
GAS
YGSSPY




3475
3476
3477
3478
3479
3480





40
75110_05K11A
GFTFSSY
GTAGD
GGFYYYGMD
SQSVSNTY
GAS
HGSSPF




3509
3510
3511
3512
3513
3514





41
75110_05L07A
GFTFSSY
NQDGSD
EGGQWLTLD
SQSVSSTY
GAS
YGSSPF




3543
3544
3545
3546
3547
3548





42
75110_06C16A
GGSISDY
YSSGS
DREDYYYYGMD
SHDISNY
AAS
YDHLPL




3577
3578
3579
3580
3581
3582





43
75110_06D16A
GGSFSGY
NHSGS
VLNWFD
SQDIADW
AAS
ANSFPY




3611
3612
3613
3614
3615
3616





44
75110_06E14A
GGSISNY
YSSGN
DREDYYYYGMD
SQDISNY
GAS
YDSLPI




3645
3646
3647
3648
3649
3650





45
75110_06G04A
GGSISSY
YISGS
ELERPYYYGMD
SQDISNY
NAS
YDNLPL




3679
3680
3681
3682
3683
3684





46
75110_06K03A
GGSISTY
NTSGS
ELERYYYYGMD
SQDISNY
YAS
YDSLPL




3713
3714
3715
3716
3717
3718





47
75110_07B16A
GGSFSGY
NQSGS
VINWFD
SQGISSW
DAS
ANSFPY




3747
3748
3749
3750
3751
3752





48
75110_07E04A
GFTFSSY
GTAGD
GGYYYYGMD
SQSISSTY
GAS
YGSSPF




3781
3782
3783
3784
3785
3786





49
75110_07H07A
GFTFSSY
KEEGSE
EGGQWLALD
SQGISSW
GAS
ANSFPW




3815
3816
3817
3818
3819
3820





50
75110_07J02A
GFTFSSY
KEDGSE
DGSYSGYGMD
SQGIRND
AAS
DYNYPY




3849
3850
3851
3852
3853
3854





51
75110_07J24A
GGSISSY
YTSGR
DEGPTDAFD
SQSLLDSDDGNTY
TLS
RIEFPF




3883
3884
3885
3886
3887
3888





52
75110_07N04A
GVSSTSF
YTSGS
DPGYSDAFA
SQDISNY
DTS
YDNLPL




3917
3918
3919
3920
3921
3922





53
75110_08A13A
GFIFSSY
KQDGSE
DNSYYYYGMD
SQGIRDD
AAS
HYNYPY




3951
3952
3953
3954
3955
3956





54
75110_08D24A
GGSISGF
YTSEN
DREGYYYYGMD
SQDISNY
AAS
YDSLPI




3985
3986
3987
3988
3989
3990





55
75110_08F20A
GGSISTY
CTTEN
DLERLNYYGMD
SQDISKY
DAS
YDSLPI




4019
4020
4021
4022
4023
4024





56
75110_08G08A
GGSISTY
CTTEN
DLERLNYYGMD
SQDISNY
DAS
YDSLPI




4053
4054
4055
4056
4057
4058





57
75110_08H06A
GFTFSNY
GTAGD
GGYDYYGMD
SQSITSIY
GAS
YGSSPF




4087
4088
4089
4090
4091
4092





58
75110_08H11A
GFTFSSY
GTAGD
GGYSYYGMD
SQSVSSTY
GAS
FGSSPF




4121
4122
4123
4124
4125
4126





59
75110_08K12A
GFTFSSY
GTAGD
GDYYYYGMD
SQSVSSTY
GAS
FGTSPF




4155
4156
4157
4158
4159
4160





60
75110_08M20A
GGSISSY
YASGS
DREGYYYYGMD
SQDISKY
AAS
YDSLPI




4189
4190
4191
4192
4193
4194





61
75110_09G15A
GFTFSDY
NQDGS
EGGQWLALD
SQGISSW
GAS
ANIFPW




4223
4224
4225
4226
4227
4228





62
75110_09N20A
GFTFSSY
NEDGSE
EGGQWLALD
SQGISSW
AAS
ANSFPW




4257
4258
4259
4260
4261
4262





63
75110_10K21A
GFTFSSY
KQDGSE
DRYDALD
SQGIRND
AAS
DYNYPY




4291
4292
4293
4294
4295
4296





64
75110_10L22A
GFTFSSY
GTAGD
GNYFYYGVD
SQSVSSSY
GAS
YGISPF




4325
4326
4327
4328
4329
4330





65
75110_10N21A
GFTFSSY
GTAGD
GGYYYYGMD
SQSFISSY
GAS
SGNSPF




4359
4360
4361
4362
4363
4364





66
75110_10016A
GFTFSNS
GTAGD
GGLYYYGMD
SQSVSSSY
GAS
FGSSPF




4393
4394
4395
4396
4397
4398





67
75110_11D03A
GFTFSSY
NQDGNE
EGGQWLALD
SQGISSW
GAS
ANSFPW




4427
4428
4429
4430
4431
4432





68
75110_12C19A
GFTFSSY
KEDGSD
EGGQWLALD
SQGISSW
GAS
ANSFPW




4461
4462
4463
4464
4465
4466





69
75110_12H17A
GFTFSDY
KEDGNE
EGGQWLALD
SQGISSW
GAS
ANSFPW




4495
4496
4497
4498
4499
4500





70
75110_12H19A
GFTFSSY
NEDGNE
EGGQWLALD
SQGISSW
GAS
ANSFPW




4529
4530
4531
4532
4533
4534





71
75110_12K21A
GGSFSGY
NHSGS
VLNYFD
SPDIANW
AAS
ANSFPL




4563
4564
4565
4566
4567
4568





72
75110_13C07A
GFTFSNY
GTAGD
GAYGYYGMD
SQSVSSSY
GAS
YGFSPF




4597
4598
4599
4600
4601
4602





73
75110_13C13A
GGSFSGY
NHSGS
VLNFFD
SPGISNW
AAS
ANSFPL




4631
4632
4633
4634
4635
4636





74
75110_13P21A
GGSFSGY
NHSGS
VLNYFD
SPDIANW
AAS
ANSFPL




4665
4666
4667
4668
4669
4670





75
75110_13P22A
GGSFSGY
NQSGN
VLNWFD
SQGISDW
AAS
ANSFPY




4699
4700
4701
4702
4703
4704





76
75110_14G10A
GFTFSSY
SSSSSY
ERGDDYGDYEGAFD
SQDISNY
DAS
YDNLPY




4733
4734
4735
4736
4737
4738





77
75110_14H13A
GFTFSNY
GTAGD
GGDYYYGMD
SQSVSSSY
GAS
FGSSPF




4767
4768
4769
4770
4771
4772





78
75110_14116A
NGSISSY
YTSGS
DREDYYYYGMD
SHDISNY
YAS
YDNLPL




4801
4802
4803
4804
4805
4806





79
75110_14N19A
GGSISRY
CTSEN
ELERLNYYGMD
SQDISNY
DAS
YDTLPI




4835
4836
4837
4838
4839
4840





80
75110_14P05A
GFTFSSY
GTAGD
GGFYYYGMD
SQSVSSSY
GAS
SGSSPF




4869
4870
4871
4872
4873
4874





81
75110_14P08A
GDSIRSY
YASGS
DGGVGDSLD
SQSLLDSDDGNTY
TLS
RIEFPF




4903
4904
4905
4906
4907
4908





82
75110_01A07A_2
GGSIINY
YSSGS
EREAYLYYGLD
SQGITNY
VTS
HNNYPL




4937
4938
4939
4940
4941
4942
















TABLE 14







AbM CDR Amino Acid Sequences of CD4 Antibodies  

















HC AbM


LC AbM



#
Protein Name
HC AbM CDR1
CDR2
HC AbM CDR3
LC AbM CDR1
CDR2
LC AbM CDR3

















1
75110_01A06A
GFTFSSYWMS
NINEDGNEKY
EGGQWLSLDY
RASQGISSWLA
GASSLQS
QQANSFPWT




2189
2190
2191
2192
2193
2194





2
75110_01A07A _1
GGSIINYYWS
RIYSSGSTN
EREAYLYYGLDV
QASQDI GNYLN
DASNLET
QQYDSLPLT




2223
2224
2225
2226
2227
2228





3
75110_01C18A
GFTVSSNYMN
VIYAGDNTY
EGGTTGAFDI
RASQGINSWLA
AASSLQS
QQGNSFPYT




2257
2258
2259
2260
2261
2262





4
75110_01D24A
GGSFSGYYWS
EINHSGSTN
LVNWFDP
RASQDISNWLA
AASSLQT
QQANSFPYS




2291
2292
2293
2294
2295
2296





5
75110_01E08A
GFTFNNYDMH
TIGTAGDTY
GGDYYYGMDV
RASQSVSSSYLA
GASSRAT
QQFGSSPFT




2325
2326
2327
2328
2329
2330





6
75110_01G11A
GFTFSSYDMH
TIGTAGDTY
GGDYYYGMDV
RASQNTYSSYLA
GASNRAT
QQHGTSPFT




2359
2360
2361
2362
2363
2364





7
75110_01H18A
GGSFSGYYWS
EINQSGSTN
VINWFDS
RASQGISSWLA
AASSFQS
QQANSFPYT




2393
2394
2395
2396
2397
2398





8
75110_01109A
GFTFSSYWMS
NTKEDGSDKY
EGGQWLALDY
RASQGISSWLA
GASSLQS
QQANSFPWT




2427
2428
2429
2430
2431
2432





9
75110_01117A
GFTFSSYDMH
TIGTADDTY
GGDYYYGMDV
RASQSVYISYLA
GASSRAT
QQFGSSPFT




2461
2462
2463
2464
2465
2466





10
75110_01K10A
GFTFRNYDMH
TIGTAGDTY
GGDYYYGMDV
RASQSLSSVYLA
GASSRAT
QQYGSSPFT




2495
2496
2497
2498
2499
2500





11
75110_01L08A
GGSISHYYWS
YIHYSGTTN
DQGFSSGGMDV
QASQDISNYLN
DASNLET
QQYDNLPLT




2529
2530
2531
2532
2533
2534





12
75110_01N04A
GFTFSNYDMH
TIGTAGDTY
GGDFYYGLDV
RASQSVSSVYLA
GASSRAT
QQYGSSPFT




2563
2564
2565
2566
2567
2568





13
75110_02E08A
GGSISTYYWT
RVYTSGDTN
DSGALYSWNYGDAFDI
RASQDISNYLA
AASSLQS
LQHNSYPRT




2597
2598
2599
2600
2601
2602





14
75110_02E22A
GGSISSFYWS
RIYTSGSTN
ELEKRNYYGMDV
QASHDISNYLN
DASTLET
QQYDSLPLT




2631
2632
2633
2634
2635
2636





15
75110_02116A
GGSFSGYYWT
EINHSGTTN
ELNWFDP
RASQDIANWLA
AASSLLG
QQANSFPYT




2665
2666
2667
2668
2669
2670





16
75110_02118A
GFTFSSYDMH
TIGTAGDTY
GGYYYYGMDV
RASQSVSSSYLA
GASSRAT
QQYGSSPFT




2699
2700
2701
2702
2703
2704





17
75110_02K11A
GGSISSGFYYW
YISYSGNTY
DRPSNFDAFDI
RASQSVSTSYLA
GASSRAT
QQYGRSPLT




T









2733
2734
2735
2736
2737
2738





18
75110_02N15A
GFTFSSYWMS
NINEDGNEKY
EGGQWLALDH
RASQGISSWLA
GASSLQS
QQANSFPWT




2767
2768
2769
2770
2771
2772





19
75110_03B16A
GFTFSSYWMS
NINEDGSEKN
EGGQWLALDY
RASQGIRSWLA
GASSLQS
QQANSFPWT




2801
2802
2803
2804
2805
2806





20
75110_03C01A
GGSFSGYYWS
EINQSGSTN
VINWFDS
RASQGISSWLA
DASSFQS
QQANSFPYT




2835
2836
2837
2838
2839
2840





21
75110_03D16A
GFTFSSYWMS
NINQDGGEKY
EGGQWLALDY
RASQGISSWLT
AASSLQS
QQANSFPWT




2869
2870
2871
2872
2873
2874





22
75110_03108A
GGSISSYYWS
YIYYSGSTN
EGEQWFYGLDV
RASQSVSSTYLA
GSSSRAT
QQYGNSFPIT




2903
2904
2905
2906
2907
2908





23
75110_03123A
GGSITSYYWN
RIYTSGSTN
DPGYSDAFNI
QASQDISNYLN
DASNLET
QQCDNLPLT




2937
2938
2939
2940
2941
2942





24
75110_03L12A
GGSFSGYYWS
EINHSGSTN
LINWFDP
RASQDISNWLA
AASSLQS
QQANSFPYT




2971
2972
2973
2974
2975
2976





25
75110_04B08A
GFNFINYGIH
IIWYDGSKKY
EDDWNDGLAY
RASQDIRNDLG
AASNLQS
LQDSNYPRT




3005
3006
3007
3008
3009
3010





26
75110_04D20A
NGSISDYYWS
RIYTSGSTN
ELERYYFYGVDV
QASQDISNYLN
AASNLET
QQYDSLPLT




3039
3040
3041
3042
3043
3044





27
75110_04F22A
GFTFSSYDIH
TIGTAGDTY
GGYYYYGMDV
RASQSVYSSYLA
GASSRAT
QQFGTSPFT




3073
3074
3075
3076
3077
3078





28
75110_04G02A
GFTFSNAWMS
RIKSKTDGGT
GGWFGELWGPFDI
KSSQSVLYSSNNKNY
WASARES
QQYFGSFPT





TD

LA






3107
3108
3109
3110
3111
3112





29
75110_04G16A
GDSISSGYYYW
YISYSGSTY
DRPSNFDAFDI
RASQSVGSTYLA
GAFSRAT
QQYGSSPLT




S









3141
3142
3143
3144
3145
3146





30
75110_04H17A
GGSISTYYWS
RIYTSERPN
ELERPYYYGMDV
QASQDISNYLN
YASNLET
QQYDNLPLT




3175
3176
3177
3178
3179
3180





31
75110_04K10A
GFTFSSYWMS
NINQDGSEKY
EGGQWLSLDY
RASQGISSWLA
GVSSFQS
QQANSFPWT




3209
3210
3211
3212
3213
3214





32
75110_04P06A
GFTFSNYDMH
TIGTAGDTY
GGDYYYGMDV
RASQSLSSVYLA
GASSRAT
QQYGSSPFT




3243
3244
3245
3246
3247
3248





33
75110_04P08A
GGSLSGYYWS
EINQSGSTN
VLNWFDP
RASQDISNWLA
AASSLQS
QQANSFPYT




3277
3278
3279
3280
3281
3282





34
75110_05A1lA
GFTFSNTWMS
RIKSKIDGGT
SGTYSSGWGLFDY
QASQDISNYLN
DTSNLEA
QQYDNLPFT





TD








3311
3312
3313
3314
3315
3316





35
75110_05B13A
GGSFSGYYWT
EINHRGSTN
PDSNWFDP
RASQDISNWLA
AASSLQS
QQANSFPLT




3345
3346
3347
3348
3349
3350





36
75110_05E05A
GGSIGSYYWS
RIYTSGSTN
DGGVGDSLDY
RSSQSLLDSDDGNTY
TLSYRAS
MQHIEFPFT







LD






3379
3380
3381
3382
3383
3384





37
75110_05E13A
GFSFSNAWMS
RVESKTDGGT
GGGFGLELYGFFDY
RASQSISSWLA
KASSLES
LQYNSYYT





TD








3413
3414
3415
3416
3417
3418





38
75110_05F19A
GFTFSNYDVH
TIGTAGDTY
GGYDYYGLDV
RASQSVSSTYLA
GASSRAT
QQYGSSPFT




3447
3448
3449
3450
3451
3452





39
75110_05G15A
GGSISSGGYFW
CIYYSGSTY
DGYDYWYFDL
RASQSVSSSYLA
GASSRAT
QQYGSSPYT




S









3481
3482
3483
3484
3485
3486





40
75110_05K11A
GFTFSSYDMH
TIGTAGDTY
GGFYYYGMDV
RASQSVSNTYLA
GASSRAT
QQHGSSPFT




3515
3516
3517
3518
3519
3520





41
75110_05L07A
GFTFSSYWMS
NINQDGSDKY
EGGQWLTLDY
RASQSVSSTYLA
GASSRAT
QQYGSSPFT




3549
3550
3551
3552
3553
3554





42
75110_06C16A
GGSISDYYWS
RIYSSGSTN
DREDYYYYGMDV
QASHDISNYLN
AASNLET
QQYDHLPLT




3583
3584
3585
3586
3587
3588





43
75110_06D16A
GGSFSGYYWS
EINHSGSTN
VLNWFDP
RASQDIADWLA
AASSFQS
QQANSFPYT




3617
3618
3619
3620
3621
3622





44
75110_06E14A
GGSISNYFWS
RIYSSGNTN
DREDYYYYGMDV
QASQDISNYLN
GASILET
QQYDSLPIT




3651
3652
3653
3654
3655
3656





45
75110_06G04A
GGSISSYYWS
RIYISGSTN
ELERPYYYGMDV
QASQDISNYLN
NASTLET
QQYDNLPLT




3685
3686
3687
3688
3689
3690





46
75110_06K03A
GGSISTYYWS
RINTSGSTT
ELERYYYYGMDV
QASQDISNYLN
YASILET
QQYDSLPLT




3719
3720
3721
3722
3723
3724





47
75110_07B16A
GGSFSGYYWS
EINQSGSTN
VINWFDS
RASQGISSWLA
DASSFQS
QQANSFPYT




3753
3754
3755
3756
3757
3758





48
75110_07E04A
GFTFSSYDMH
TIGTAGDTY
GGYYYYGMDV
RASQSISSTYLA
GASSRAT
QQYGSSPFT




3787
3788
3789
3790
3791
3792





49
75110_07H07A
GFTFSSYWMS
NIKEEGSEKY
EGGQWLALDY
RASQGISSWLA
GASSLQS
QQANSFPWT




3821
3822
3823
3824
3825
3826





50
75110_07J02A
GFTFSSYWMS
NIKEDGSEKY
DGSYSGYGMDV
RASQGIRNDLG
AASSLQS
LLDYNYPYT




3855
3856
3857
3858
3859
3860





51
75110_07J24A
GGSISSYYYN
RIYTSGRTD
DEGPTDAFDI
RSSQSLLDSDDGNTY
TLSYRAS
MQRIEFPFT







LD






3889
3890
3891
3892
3893
3894





52
75110_07N04A
GVSSTSFYWS
RIYTSGSTN
DPGYSDAFAI
QASQDISNYLT
DTSNLET
QQYDNLPLT




3923
3924
3925
3926
3927
3928





53
75110_08A13A
GFIFSSYWMS
NIKQDGSEKY
DNSYYYYGMDV
RASQGIRDDLG
AASSLQS
LHHYNYPYT




3957
3958
3959
3960
3961
3962





54
75110_08D24A
GGSISGFYWS
RIYTSENTN
DREGYYYYGMDV
QASQDISNYLN
AASNLET
QQYDSLPIT




3991
3992
3993
3994
3995
3996





55
75110_08F20A
GGSISTYYWS
RICTTENTN
DLERLNYYGMDV
QASQDISKYLN
DASNLET
QQYDSLPIT




4025
4026
4027
4028
4029
4030





56
75110_08G08A
GGSISTYYWS
RICTTENTN
DLERLNYYGMDV
QASQDISNYLN
DASNLET
QQYDSLPIT




4059
4060
4061
4062
4063
4064





57
75110_08H06A
GFTFSNYDMH
TIGTAGDTY
GGYDYYGMDV
RASQSITSIYLA
GASSRAT
QQYGSSPFT




4093
4094
4095
4096
4097
4098





58
75110_08H11A
GFTFSSYDMH
TIGTAGDTY
GGYSYYGMDV
GASQSVSSTYLA
GASSRAT
QQFGSSPFT




4127
4128
4129
4130
4131
4132





59
75110_08K12A
GFTFSSYDMH
TIGTAGDTY
GDYYYYGMDV
RASQSVSSTYLA
GASNRAT
QQFGTSPFT




4161
4162
4163
4164
4165
4166





60
75110_08M20A
GGSISSYYWS
RIYASGSTN
DREGYYYYGMDV
QASQDISKYLN
AASNLET
QQYDSLPIT




4195
4196
4197
4198
4199
4200





61
75110_09G15A
GFTFSDYWMS
NINQDGSEK
EGGQWLALDY
RASQGISSWLA
GASSLQS
QQANIFPWT




4229
4230
4231
4232
4233
4234





62
75110_09N20A
GFTFSSYWMS
NINEDGSEKY
EGGQWLALDY
RASQGISSWLA
AASSLQS
QQANSFPWT




4263
4264
4265
4266
4267
4268





63
75110_10K21A
GFTFSSYWMT
NIKQDGSEKY
DRYDALDI
RASQGIRNDLN
AASSLQS
LKDYNYPYT




4297
4298
4299
4300
4301
4302





64
75110_10L22A
GFTFSSYDMH
TIGTAGDTY
GNYFYYGVDV
RASQSVSSSYLA
GASSRAT
QQYGISPFT




4331
4332
4333
4334
4335
4336





65
75110_10N21A
GFTFSSYDMH
TIGTAGDTY
GGYYYYGMDV
RASQSFISSYLA
GASSRAT
QQSGNSPFT




4365
4366
4367
4368
4369
4370





66
75110_10016A
GFTFSNSDMH
TIGTAGDTY
GGLYYYGMDV
RASQSVSSSYLA
GASSRAT
HQFGSSPFT




4399
4400
4401
4402
4403
4404





67
75110_11D03A
GFTFSSYWMS
NINQDGNEKY
EGGQWLALDY
RASQGISSWLA
GASSLQS
QQANSFPWT




4433
4434
4435
4436
4437
4438





68
75110_12C19A
GFTFSSYWMS
NIKEDGSDKY
EGGQWLALDY
RASQGISSWLA
GASSLQS
QQANSFPWT




4467
4468
4469
4470
4471
4472





69
75110_12H17A
GFTFSDYWMS
NIKEDGNEKY
EGGQWLALDY
RASQGISSWLA
GASSLQS
QQANSFPWT




4501
4502
4503
4504
4505
4506





70
75110_12H19A
GFTFSSYWMS
NINEDGNEKY
EGGQWLALDY
RASQGISSWLA
GASGLQS
QQANSFPWT




4535
4536
4537
4538
4539
4540





71
75110_12K21A
GGSFSGYYWS
EINHSGSTN
VLNYFDY
RASPDIANWLA
AASSLQS
QQANSFPLT




4569
4570
4571
4572
4573
4574





72
75110_13C07A
GFTFSNYDMH
TIGTAGDTY
GAYGYYGMDV
RASQSVSSSYLA
GASSRAT
QQYGFSPFT




4603
4604
4605
4606
4607
4608





73
75110_13C13A
GGSFSGYYWS
EINHSGSTN
VLNFFDY
RASPGISNWLA
AASSLQS
QQANSFPLT




4637
4638
4639
4640
4641
4642





74
75110_13P21A
GGSFSGYYWS
EINHSGSTN
VLNYFDY
RASPDIANWLA
AASSLQS
QQANSFPLT




4671
4672
4673
4674
4675
4676





75
75110_13P22A
GGSFSGYYWS
EINQSGNTN
VLNWFDY
RASQGISDWLA
AASSLQS
QQANSFPYT




4705
4706
4707
4708
4709
4710





76
75110_14G10A
GFTFSSYSMN
FISSSSSYIY
ERGDDYGDYEGAFDI
QASQDISNYLN
DASNLET
QQYDNLPYT




4739
4740
4741
4742
4743
4744





77
75110_14H13A
GFTFSNYDMH
TIGTAGDTY
GGDYYYGMDV
RASQSVSSSYLA
GASSRAT
QQFGSSPFT




4773
4774
4775
4776
4777
4778





78
75110_14116A
NGSISSYYWS
RIYTSGSTN
DREDYYYYGMDV
QASHDISNYLN
YASNLET
QQYDNLPLT




4807
4808
4809
4810
4811
4812





79
75110_14N19A
GGSISRYYWS
RICTSENPN
ELERLNYYGMDV
QASQDISNYLN
DASNLES
QQYDTLPIT




4841
4842
4843
4844
4845
4846





80
75110_14P05A
GFTFSSYDVH
TIGTAGDTY
GGFYYYGMDV
RASQSVSSSYLA
GASSRAT
QQSGSSPFT




4875
4876
4877
4878
4879
4880





81
75110_14P08A
GDSIRSYYWN
RIYASGSTN
DGGVGDSLDY
RSSQSLLDSDDGNTY
TLSYRAS
MQRIEFPFT







LD






4909
4910
4911
4912
4913
4914





82
75110_01A07A_2
GGSIINYYWS
RIYSSGSTN
EREAYLYYGLDV
RASQGITNYLA
VTSSFQS
LQHNNYPLT




4943
4944
4945
4946
4947
4948
















TABLE 15







Contact CDR Amino Acid Sequences of CD4 Antibodies
















HC Contact
HC Contact
HC Contact
LC Contact
LC Contact
LC Contact


#
Protein Name
CDR1
CDR2
CDR3
CDR1
CDR2
CDR3

















1
75110_01A06A
SSYWMS
WVANINEDGNEKY
AREGGQWLSLD
SSWLAWY
ILIYGASSLQ
QQANSFPW




2195
2196
2197
2198
2199
2200





2
75110_01A07A_1
INYYWS
WIGRIYSSGSTN
AREREAYLYYGLD
GNYLNWY
LLIYDASNLE
QQYDSLPL




2229
2230
2231
2232
2233
2234





3
75110_01C18A
SSNYMN
WVSVIYAGDNTY
AREGGTTGAFD
NSWLAWY
LLIYAASSLQ
QQGNSFPY




2263
2264
2265
2266
2267
2268





4
75110_01D24A
SGYYWS
WIGEINHSGSTN
ARLVNWFD
SNWLAWY
LLIFAASSLQ
QQANSFPY




2297
2298
2299
2300
2301
2302





5
75110_01E08A
NNYDMH
WVSTIGTAGDTY
ARGGDYYYGMD
SSSYLAWY
LLIYGASSRA
QQFGSSPF




2331
2332
2333
2334
2335
2336





6
75110_01G11A
SSYDMH
WVSTIGTAGDTY
ARGGDYYYGMD
YSSYLAWY
LLIYGASNRA
QQHGTSPF




2365
2366
2367
2368
2369
2370





7
75110_01H18A
SGYYWS
WIGEINQSGSTN
ARVINWFD
SSWLAWY
LLIYAASSFQ
QQANSFPY




2399
2400
2401
2402
2403
2404





8
75110_01109A
SSYWMS
WVANTKEDGSDKY
AREGGQWLALD
SSWLAWY
LLIFGASSLQ
QQANSFPW




2433
2434
2435
2436
2437
2438





9
75110_01117A
SSYDMH
WVSTIGTADDTY
ARGGDYYYGMD
YISYLAWY
LLIYGASSRA
QQFGSSPF




2467
2468
2469
2470
2471
2472





10
75110_01K10A
RNYDMH
WVSTIGTAGDTY
ARGGDYYYGMD
SSVYLAWY
LLIYGASSRA
QQYGSSPF




2501
2502
2503
2504
2505
2506





11
75110_01L08A
SHYYWS
WIGYIHYSGTTN
ARDQGFSSGGMD
SNYLNWY
LLIYDASNLE
QQYDNLPL




2535
2536
2537
2538
2539
2540





12
75110_01NO4A
SNYDMH
WVSTIGTAGDTY
ARGGDFYYGLD
SSVYLAWY
LLIYGASSRA
QQYGSSPF




2569
2570
2571
2572
2573
2574





13
75110_02E08A
STYYWT
WIGRVYTSGDTN
ARDSGALYSWNYGD
SNYLAWF
RLIYAASSLQ
LQHNSYPR






AFD







2603
2604
2605
2606
2607
2608





14
75110_02E22A
SSFYWS
WIGRIYTSGSTN
ARELEKRNYYGMD
SNYLNWY
LLIFDASTLE
QQYDSLPL




2637
2638
2639
2640
2641
2642





15
75110_02116A
SGYYWT
WIGEINHSGTTN
TRELNWFD
ANWLAWY
LLIYAASSLL
QQANSFPY




2671
2672
2673
2674
2675
2676





16
75110_02118A
SSYDMH
WVSTIGTAGDTY
ARGGYYYYGMD
SSSYLAWY
LLIHGASSRA
QQYGSSPF




2705
2706
2707
2708
2709
2710





17
75110_02K11A
SSGFYYWT
WIGYISYSGNTY
ARDRPSNFDAFD
STSYLAWY
LLIYGASSRA
QQYGRSPL




2739
2740
2741
2742
2743
2744





18
75110_02N15A
SSYWMS
WVANINEDGNEKY
AREGGQWLALD
SSWLAWY
FLISGASSLQ
QQANSFPW




2773
2774
2775
2776
2777
2778





19
75110_03B16A
SSYWMS
WVANINEDGSEKN
AREGGQWLALD
RSWLAWY
LLICGASSLQ
QQANSFPW




2807
2808
2809
2810
2811
2812





20
75110_03C01A
SGYYWS
WIGEINQSGSTN
ARVINWFD
SSWLAWY
LLIYDASSFQ
QQANSFPY




2841
2842
2843
2844
2845
2846





21
75110_03D16A
SSYWMS
WVANINQDGGEKY
VREGGQWLALD
SSWLTWY
FLIYAASSLQ
QQANSFPW




2875
2876
2877
2878
2879
2880





22
75110_03108A
SSYYWS
WIGYIYYSGSTN
AREGEQWFYGLD
SSTYLAWY
LLIYGSSSRA
QQYGNSFPI




2909
2910
2911
2912
2913
2914





23
75110_03123A
TSYYWN
WIGRIYTSGSTN
ARDPGYSDAFN
SNYLNWY
LLIYDASNLE
QQCDNLPL




2943
2944
2945
2946
2947
2948





24
75110_03L12A
SGYYWS
WIGEINHSGSTN
VRLINWFD
SNWLAWY
LLIFAASSLQ
QQANSFPY




2977
2978
2979
2980
2981
2982





25
75110_04B08A
INYGIH
WVTIIWYDGSKKY
AREDDWNDGLA
RNDLGWY
LLIYAASNLQ
LQDSNYPR




3011
3012
3013
3014
3015
3016





26
75110_04D20A
SDYYWS
WIGRIYTSGSTN
ARELERYYFYGVD
SNYLNWY
LLIYAASNLE
QQYDSLPL




3045
3046
3047
3048
3049
3050





27
75110_04F22A
SSYDIH
WVSTIGTAGDTY
ARGGYYYYGMD
YSSYLAWY
LLIYGASSRA
QQFGTSPF




3079
3080
3081
3082
3083
3084





28
75110_04G02A
SNAWMS
WVGRIKSKIDGGITD
TTGGWFGELWGPFD
LYSSNNKNYLAWY
LLFYWASARE
QQYFGSFP




3113
3114
3115
3116
3117
3118





29
75110_04G16A
SSGYYYWS
WIGYISYSGSTY
ARDRPSNFDAFD
GSTYLAWY
LLIYGAFSRA
QQYGSSPL




3147
3148
3149
3150
3151
3152





30
75110_04H17A
STYYWS
WIGRIYTSERPN
ARELERPYYYGMD
SNYLNWY
LLIYYASNLE
QQYDNLPL




3181
3182
3183
3184
3185
3186





31
75110_04K10A
SSYWMS
WVANINQDGSEKY
AREGGQWLSLD
SSWLAWY
VLIYGVSSFQ
QQANSFPW




3215
3216
3217
3218
3219
3220





32
75110_04P06A
SNYDMH
WVSTIGTAGDTY
ARGGDYYYGMD
SSVYLAWY
LLIYGASSRA
QQYGSSPF




3249
3250
3251
3252
3253
3254





33
75110_04P08A
SGYYWS
WIGEINQSGSTN
TRVLNWFD
SNWLAWY
LLIYAASSLQ
QQANSFPY




3283
3284
3285
3286
3287
3288





34
75110_05A11A
SNTWMS
WVGRIKSKIDGGTTD
TTSGTYSSGWGLFD
SNYLNWY
LLIYDTSNLE
QQYDNLPF




3317
3318
3319
3320
3321
3322





35
75110_05B13A
SGYYWT
WIGEINHRGSTN
TRPDSNWFD
SNWLAWY
LLIFAASSLQ
QQANSFPL




3351
3352
3353
3354
3355
3356





36
75110_05E05A
GSYYWS
WIGRIYTSGSTN
ATDGGVGDSLD
LDSDDGNTYLDWY
LLIYTLSYRA
MQHIEFPF




3385
3386
3387
3388
3389
3390





37
75110_05E13A
SNAWMS
WVGRVESKTDGGTTD
TIGGGFGLELYGFF
SSWLAWY
LLIYKASSLE
LQYNSYY






D







3419
3420
3421
3422
3423
3424





38
75110_05F19A
SNYDVH
WVSTIGTAGDTY
ARGGYDYYGLD
SSTYLAWY
LLIFGASSRA
QQYGSSPF




3453
3454
3455
3456
3457
3458





39
75110_05G15A
SSGGYFWS
WIGCIYYSGSTY
ARDGYDYWYFD
SSSYLAWY
LLIYGASSRA
QQYGSSPY




3487
3488
3489
3490
3491
3492





40
75110_05K11A
SSYDMH
WVSTIGTAGDTY
ARGGFYYYGMD
SNTYLAWY
LLIYGASSRA
QQHGSSPF




3521
3522
3523
3524
3525
3526





41
75110_05L07A
SSYWMS
WVANINQDGSDKY
AREGGQWLTLD
SSTYLAWY
LLIFGASSRA
QQYGSSPF




3555
3556
3557
3558
3559
3560





42
75110_06C16A
SDYYWS
WIGRIYSSGSTN
ARDREDYYYYGMD
SNYLNWY
LLIYAASNLE
QQYDHLPL




3589
3590
3591
3592
3593
3594





43
75110_06D16A
SGYYWS
WIGEINHSGSTN
ARVLNWFD
ADWLAWY
LLIYAASSFQ
QQANSFPY




3623
3624
3625
3626
3627
3628





44
75110_06E14A
SNYFWS
WIGRIYSSGNTN
ARDREDYYYYGMD
SNYLNWY
LLIYGASILE
QQYDSLPI




3657
3658
3659
3660
3661
3662





45
75110_06G04A
SSYYWS
WIGRIYISGSTN
ARELERPYYYGMD
SNYLNWY
LLIYNASTLE
QQYDNLPL




3691
3692
3693
3694
3695
3696





46
75110_06K03A
STYYWS
WIGRINTSGSTT
ARELERYYYYGMD
SNYLNWY
LLIYYASILE
QQYDSLPL




3725
3726
3727
3728
3729
3730





47
75110_07B16A
SGYYWS
WIGEINQSGSTN
ARVINWFD
SSWLAWY
LLIYDASSFQ
QQANSFPY




3759
3760
3761
3762
3763
3764





48
75110_07E04A
SSYDMH
WVSTIGTAGDTY
ARGGYYYYGMD
SSTYLAWY
LLIYGASSRA
QQYGSSPF




3793
3794
3795
3796
3797
3798





49
75110_07H07A
SSYWMS
WVANIKEEGSEKY
VREGGQWLALD
SSWLAWY
LLIFGASSLQ
QQANSFPW




3827
3828
3829
3830
3831
3832





50
75110_07J02A
SSYWMS
WVANIKEDGSEKY
ARDGSYSGYGMD
RNDLGWY
LLIYAASSLQ
LLDYNYPY




3861
3862
3863
3864
3865
3866





51
75110_07J24A
SSYYYN
WIGRIYTSGRTD
ARDEGPTDAFD
LDSDDGNTYLDWY
LLIYTLSYRA
MQRIEFPF




3895
3896
3897
3898
3899
3900





52
75110_07N04A
TSFYWS
WIGRIYTSGSTN
ARDPGYSDAFA
SNYLTWY
LLIYDTSNLE
QQYDNLPL




3929
3930
3931
3932
3933
3934





53
75110_08A13A
SSYWMS
WVANIKQDGSEKY
ARDNSYYYYGMD
RDDLGWY
LLIFAASSLQ
LHHYNYPY




3963
3964
3965
3966
3967
3968





54
75110_08D24A
SGFYWS
WIGRIYTSENTN
ARDREGYYYYGMD
SNYLNWY
LLIYAASNLE
QQYDSLPI




3997
3998
3999
4000
4001
4002





55
75110_08F20A
STYYWS
WIGRICTTENTN
ARDLERLNYYGMD
SKYLNWY
LLIYDASNLE
QQYDSLPI




4031
4032
4033
4034
4035
4036





56
75110_08G08A
STYYWS
WIGRICTTENTN
ARDLERLNYYGMD
SNYLNWY
LLIYDASNLE
QQYDSLPI




4065
4066
4067
4068
4069
4070





57
75110_08H06A
SNYDMH
WVSTIGTAGDTY
ARGGYDYYGMD
TSIYLAWY
LLIYGASSRA
QQYGSSPF




4099
4100
4101
4102
4103
4104





58
75110_08H11A
SSYDMH
WVSTIGTAGDTY
ARGGYSYYGMD
SSTYLAWY
LLIYGASSRA
QQFGSSPF




4133
4134
4135
4136
4137
4138





59
75110_08K12A
SSYDMH
WVSTIGTAGDTY
ARGDYYYYGMD
SSTYLAWY
LLIYGASNRA
QQFGTSPF




4167
4168
4169
4170
4171
4172





60
75110_08M20A
SSYYWS
WIGRIYASGSTN
ARDREGYYYYGMD
SKYLNWY
LLIYAASNLE
QQYDSLPI




4201
4202
4203
4204
4205
4206





61
75110_09G15A
SDYWMS
WVANINQDGSEK
AREGGQWLALD
SSWLAWY
LLIYGASSLQ
QQANIFPW




4235
4236
4237
4238
4239
4240





62
75110_09N20A
SSYWMS
WVANINEDGSEKY
VREGGQWLALD
SSWLAWY
LLIYAASSLQ
QQANSFPW




4269
4270
4271
4272
4273
4274





63
75110_10K21A
SSYWMT
WVANIKQDGSEKY
VRDRYDALD
RNDLNWY
LLIYAASSLQ
LKDYNYPY




4303
4304
4305
4306
4307
4308





64
75110_10L22A
SSYDMH
WVSTIGTAGDTY
ARGNYFYYGVD
SSSYLAWY
LLIYGASSRA
QQYGISPF




4337
4338
4339
4340
4341
4342





65
75110_10N21A
SSYDMH
WVSTIGTAGDTY
ARGGYYYYGMD
ISSYLAWY
LLIYGASSRA
QQSGNSPF




4371
4372
4373
4374
4375
4376





66
75110_10016A
SNSDMH
WVSTIGTAGDTY
ARGGLYYYGMD
SSSYLAWY
LLIYGASSRA
HQFGSSPF




4405
4406
4407
4408
4409
4410





67
75110_11D03A
SSYWMS
WVANINQDGNEKY
AREGGQWLALD
SSWLAWY
FLISGASSLQ 
QQANSFPW




4439
4440
4441
4442
4443
4444





68
75110_12C19A
SSYWMS
WVANIKEDGSDKY
VREGGQWLALD
SSWLAWY
LLIYGASSLQ
QQANSFPW




4473
4474
4475
4476
4477
4478





69
75110_12H17A
SDYWMS
WVANIKEDGNEKY
AREGGQWLALD
SSWLAWY
FLISGASSLQ 
QQANSFPW




4507
4508
4509
4510
4511
4512





70
75110_12H19A
SSYWMS
WVANINEDGNEKY
AREGGQWLALD
SSWLAWY
LLIYGASGLQ
QQANSFPW




4541
4542
4543
4544
4545
4546





71
75110_12K21A
SGYYWS
WIGEINHSGSTN
ARVLNYFD
ANWLAWY
LL IYAASSLQ
QQANSFPL




4575
4576
4577
4578
4579
4580





72
75110_13C07A
SNYDMH
WVSTIGTAGDTY
ARGAYGYYGMD
SSSYLAWY
LLIYGASSRA
QQYGFSPF




4609
4610
4611
4612
4613
4614





73
75110_13C13A
SGYYWS
WIGEINHSGSTN
ARVLNFFD
SNWLAWY
LLIYAASSLQ
QQANSFPL




4643
4644
4645
4646
4647
4648





74
75110_13P21A
SGYYWS
WIGEINHSGSTN
ARVLNYFD
ANWLAWY
LLIYAASSLQ
QQANSFPL




4677
4678
4679
4680
4681
4682





75
75110_13P22A
SGYYWS
WIGEINQSGNTN
ARVLNWFD
SDWLAWY
LLIFAASSLQ
QQANSFPY




4711
4712
4713
4714
4715
4716





76
75110_14G10A
SSYSMN
WVSFISSSSSYIY
ARERGDDYGDYEGA
SNYLNWY
LLIYDASNLE
QQYDNLPY






FD







4745
4746
4747
4748
4749
4750





77
75110_14H13A
SNYDMH
WVSTIGTAGDTY
ARGGDYYYGMD
SSSYLAWY
LLIYGASSRA
QQFGSSPF




4779
4780
4781
4782
4783
4784





78
75110_14116A
SSYYWS
WIGRIYTSGSTN
ARDREDYYYYGMD
SNYLNWY
LLLYYASNLE
QQYDNLPL




4813
4814
4815
4816
4817
4818





79
75110_14N19A
SRYYWS
WIGRICTSENPN
ARELERLNYYGMD
SNYLNWY
LLIYDASNLE
QQYDTLPI




4847
4848
4849
4850
4851
4852





80
75110_14P05A
SSYDVH
WVSTIGTAGDTY
ARGGFYYYGMD
SSSYLAWY
LLIYGASSRA
QQSGSSPF




4881
4882
4883
4884
4885
4886





81
75110_14P08A
RSYYWN
WIGRIYASGSTN
ARDGGVGDSLD
LDSDDGNTYLDWY
LLIYTLSYRA
MQRIEFPF




4915
4916
4917
4918
4919
4920





82
75110_01A07A_2
INYYWS
WIGRIYSSGSTN
AREREAYLYYGLD
TNYLAWF
RLIYVTS SFQ
LQHNNYPL




4949
4950
4951
4952
4953
4954
















TABLE 16







IMGT CDR Amino Acid Sequences of CD4 Antibodies
















HC IMGT
HC IMGT

LC IMGT
LC IMGT
LC IMGT


#
Protein Name
CDR1
CDR2
HC IMGT CDR3
CDR1
CDR2
CDR3

















1
75110_01A06A
GFTFSSYW
INEDGNEK
AREGGQWLSLDY
QGISSW
GAS
QQANSFPWT




2201
2202
2203
2204
2205
2206





2
75110_01A07A_1
GGSIINYY
IYSSGST
AREREAYLYYGLDV
QDIGNY
DAS
QQYDSLPLT




2235
2236
2237
2238
2239
2240





3
75110_01C18A
GFTVSSNY
IYAGDNT
AREGGTTGAFDI
QGINSW
AAS
QQGNSFPYT




2269
2270
2271
2272
2273
2274





4
75110_01D24A
GGSFSGYY
INHSGST
ARLVNWFDP
QDISNW
AAS
QQANSFPYS




2303
2304
2305
2306
2307
2308





5
75110_01E08A
GFTFNNYD
IGTAGDT
ARGGDYYYGMDV
QSVSSSY
GAS
QQFGSSPFT




2337
2338
2339
2340
2341
2342





6
75110_01G11A
GFTFSSYD
IGTAGDT
ARGGDYYYGMDV
QNTYSSY
GAS
QQHGTSPFT




2371
2372
2373
2374
2375
2376





7
75110_01H18A
GGSFSGYY
INQSGST
ARVINWFDS
QGISSW
AAS
QQANSFPYT




2405
2406
2407
2408
2409
2410





8
75110_01109A
GFTFSSYW
TKEDGSDK
AREGGQWLALDY
QGISSW
GAS
QQANSFPWT




2439
2440
2441
2442
2443
2444





9
75110_01117A
GFTFSSYD
IGTADDT
ARGGDYYYGMDV
QSVYISY
GAS
QQFGSSPFT




2473
2474
2475
2476
2477
2478





10
75110_01K10A
GFTFRNYD
IGTAGDT
ARGGDYYYGMDV
QSLSSVY
GAS
QQYGSSPFT




2507
2508
2509
2510
2511
2512





11
75110_01L08A
GGSISHYY
IHYSGTT
ARDQGFSSGGMDV
QDISNY
DAS
QQYDNLPLT




2541
2542
2543
2544
2545
2546





12
75110_01N04A
GFTFSNYD
IGTAGDT
ARGGDFYYGLDV
QSVSSVY
GAS
QQYGSSPFT




2575
2576
2577
2578
2579
2580





13
75110_02E08A
GGSISTYY
VYTSGDT
ARDSGALYSWNYGDAFDI
QDISNY
AAS
LQHNSYPRT




2609
2610
2611
2612
2613
2614





14
75110_02E22A
GGSISSFY
IYTSGST
ARELEKRNYYGMDV
HDISNY
DAS
QQYDSLPLT




2643
2644
2645
2646
2647
2648





15
75110_02116A
GGSFSGYY
INHSGTT
TRELNWFDP
QDIANW
AAS
QQANSFPYT




2677
2678
2679
2680
2681
2682





16
75110_02118A
GFTFSSYD
IGTAGDT
ARGGYYYYGMDV
QSVSSSY
GAS
QQYGSSPFT




2711
2712
2713
2714
2715
2716





17
75110_02K11A
GGSISSGFY
ISYSGNT
ARDRPSNFDAFDI
QSVSTSY
GAS
QQYGRSPLT




Y









2745
2746
2747
2748
2749
2750





18
75110_02N15A
GFTFSSYW
INEDGNEK
AREGGQWLALDH
QGISSW
GAS
QQANSFPWT




2779
2780
2781
2782
2783
2784





19
75110_03B16A
GFTFSSYW
INEDGSEK
AREGGQWLALDY
QGIRSW
GAS
QQANSFPWT




2813
2814
2815
2816
2817
2818





20
75110_03C01A
GGSFSGYY
INQSGST
ARVINWFDS
QGISSW
DAS
QQANSFPYT




2847
2848
2849
2850
2851
2852





21
75110_03D16A
GFTFSSYW
INQDGGEK
VREGGQWLALDY
QGISSW
AAS
QQANSFPWT




2881
2882
2883
2884
2885
2886





22
75110_03108A
GGSISSYY
IYYSGST
AREGEQWFYGLDV
QSVSSTY
GSS
QQYGNSFPIT




2915
2916
2917
2918
2919
2920





23
75110_03123A
GGSITSYY
IYTSGST
ARDPGYSDAFNI
QDISNY
DAS
QQCDNLPLT




2949
2950
2951
2952
2953
2954





24
75110_03L12A
GGSFSGYY
INHSGST
VRLINWFDP
QDISNW
AAS
QQANSFPYT




2983
2984
2985
2986
2987
2988





25
75110_04B08A
GFNFINYG
IWYDGSKK
AREDDWNDGLAY
QDIRND
AAS
LQDSNYPRT




3017
3018
3019
3020
3021
3022





26
75110_04D20A
NGSISDYY
IYTSGST
ARELERYYFYGVDV
QDISNY
AAS
QQYDSLPLT




3051
3052
3053
3054
3055
3056





27
75110_04F22A
GFTFSSYD
IGTAGDT
ARGGYYYYGMDV
QSVYSSY
GAS
QQFGTSPFT




3085
3086
3087
3088
3089
3090





28
75110_04G02A
GFTFSNAW
IKSKTDGGTT
TTGGWFGELWGPFDI
QSVLYSSNNKNY
WAS
QQYFGSFPT




3119
3120
3121
3122
3123
3124





29
75110_04G16A
GDSISSGYY
ISYSGST
ARDRPSNFDAFDI
QSVGSTY
GAF
QQYGSSPLT




Y









3153
3154
3155
3156
3157
3158





30
75110_04H17A
GGSISTYY
IYTSERP
ARELERPYYYGMDV
QDISNY
YAS
QQYDNLPLT




3187
3188
3189
3190
3191
3192





31
75110_04K10A
GFTFSSYW
INQDGSEK
AREGGQWLSLDY
QGISSW
GVS
QQANSFPWT




3221
3222
3223
3224
3225
3226





32
75110_04P06A
GFTFSNYD
IGTAGDT
ARGGDYYYGMDV
QSLSSVY
GAS
QQYGSSPFT




3255
3256
3257
3258
3259
3260





33
75110_04P08A
GGSLSGYY
INQSGST
TRVLNWFDP
QDISNW
AAS
QQANSFPYT




3289
3290
3291
3292
3293
3294





34
75110_05A11A
GFTFSNTW
IKSKIDGGTT
TTSGTYSSGWGLFDY
QDISNY
DTS
QQYDNLPFT




3323
3324
3325
3326
3327
3328





35
75110_05B13A
GGSFSGYY
INHRGST
TRPDSNWFDP
QDISNW
AAS
QQANSFPLT




3357
3358
3359
3360
3361
3362





36
75110_05E05A
GGSIGSYY
IYTSGST
ATDGGVGDSLDY
QSLLDSDDGNTY
TLS
MQHIEFPFT




3391
3392
3393
3394
3395
3396





37
75110_05E13A
GFSFSNAW
VESKTDGGTT
TIGGGFGLELYGFFDY
QSISSW
KAS
LQYNSYYT




3425
3426
3427
3428
3429
3430





38
75110_05F19A
GFTFSNYD
IGTAGDT
ARGGYDYYGLDV
QSVSSTY
GAS
QQYGSSPFT




3459
3460
3461
3462
3463
3464





39
75110_05G15A
GGSISSGGY
IYYSGST
ARDGYDYWYFDL
QSVSSSY
GAS
QQYGSSPYT




F









3493
3494
3495
3496
3497
3498





40
75110_05K11A
GFTFSSYD
IGTAGDT
ARGGFYYYGMDV
QSVSNTY
GAS
QQHGSSPFT




3527
3528
3529
3530
3531
3532





41
75110_05L07A
GFTFSSYW
INQDGSDK
AREGGQWLTLDY
QSVSSTY
GAS
QQYGSSPFT




3561
3562
3563
3564
3565
3566





42
75110_06C16A
GGSISDYY
IYSSGST
ARDREDYYYYGMDV
HDISNY
AAS
QQYDHLPLT




3595
3596
3597
3598
3599
3600





43
75110_06D16A
GGSFSGYY
INHSGST
ARVLNWFDP
QDIADW
AAS
QQANSFPYT




3629
3630
3631
3632
3633
3634





44
75110_06E14A
GGSISNYF
IYSSGNT
ARDREDYYYYGMDV
QDISNY
GAS
QQYDSLPIT




3663
3664
3665
3666
3667
3668





45
75110_06G04A
GGSISSYY
IYISGST
ARELERPYYYGMDV
QDISNY
NAS
QQYDNLPLT




3697
3698
3699
3700
3701
3702





46
75110_06K03A
GGSISTYY
INTSGST
ARELERYYYYGMDV
QDISNY
YAS
QQYDSLPLT




3731
3732
3733
3734
3735
3736





47
75110_07B16A
GGSFSGYY
INQSGST
ARVINWFDS
QGISSW
DAS
QQANSFPYT




3765
3766
3767
3768
3769
3770





48
75110_07E04A
GFTFSSYD
IGTAGDT
ARGGYYYYGMDV
QSISSTY
GAS
QQYGSSPFT




3799
3800
3801
3802
3803
3804





49
75110_07H07A
GFTFSSYW
IKEEGSEK
VREGGQWLALDY
QGISSW
GAS
QQANSFPWT




3833
3834
3835
3836
3837
3838





50
75110_07J02A
GFTFSSYW
IKEDGSEK
ARDGSYSGYGMDV
QGIRND
AAS
LLDYNYPYT




3867
3868
3869
3870
3871
3872





51
75110_07J24A
GGSISSYY
IYTSGRT
ARDEGPTDAFDI
QSLLDSDDGNTY
TLS
MQRIEFPFT




3901
3902
3903
3904
3905
3906





52
75110_07N04A
GVSSTSFY
IYTSGST
ARDPGYSDAFAI
QDISNY
DTS
QQYDNLPLT




3935
3936
3937
3938
3939
3940





53
75110_08A13A
GFIFSSYW
IKQDGSEK
ARDNSYYYYGMDV
QGIRDD
AAS
LHHYNYPYT




3969
3970
3971
3972
3973
3974





54
75110_08D24A
GGSISGFY
IYTSENT
ARDREGYYYYGMDV
QDISNY
AAS
QQYDSLPIT




4003
4004
4005
4006
4007
4008





55
75110_08F20A
GGSISTYY
ICTTENT
ARDLERLNYYGMDV
QDISKY
DAS
QQYDSLPIT




4037
4038
4039
4040
4041
4042





56
75110_08G08A
GGSISTYY
ICTTENT
ARDLERLNYYGMDV
QDISNY
DAS
QQYDSLPIT




4071
4072
4073
4074
4075
4076





57
75110_08H06A
GFTFSNYD
IGTAGDT
ARGGYDYYGMDV
QSITSIY
GAS
QQYGSSPFT




4105
4106
4107
4108
4109
4110





58
75110_08H11A
GFTFSSYD
IGTAGDT
ARGGYSYYGMDV
QSVSSTY
GAS
QQFGSSPFT




4139
4140
4141
4142
4143
4144





59
75110_08K12A
GFTFSSYD
IGTAGDT
ARGDYYYYGMDV
QSVSSTY
GAS
QQFGTSPFT




4173
4174
4175
4176
4177
4178





60
75110_08M20A
GGSISSYY
IYASGST
ARDREGYYYYGMDV
QDISKY
AAS
QQYDSLPIT




4207
4208
4209
4210
4211
4212





61
75110_09G15A
GFTFSDYW
INQDGSE
AREGGQWLALDY
QGISSW
GAS
QQANIFPWT




4241
4242
4243
4244
4245
4246





62
75110_09N20A
GFTFSSYW
INEDGSEK
VREGGQWLALDY
QGISSW
AAS
QQANSFPWT




4275
4276
4277
4278
4279
4280





63
75110_10K21A
GFTFSSYW
IKQDGSEK
VRDRYDALDI
QGIRND
AAS
LKDYNYPYT




4309
4310
4311
4312
4313
4314





64
75110_10L22A
GFTFSSYD
IGTAGDT
ARGNYFYYGVDV
QSVSSSY
GAS
QQYGISPFT




4343
4344
4345
4346
4347
4348





65
75110_10N21A
GFTFSSYD
IGTAGDT
ARGGYYYYGMDV
QSFISSY
GAS
QQSGNSPFT




4377
4378
4379
4380
4381
4382





66
75110_10016A
GFTFSNSD
IGTAGDT
ARGGLYYYGMDV
QSVSSSY
GAS
HQFGSSPFT




4411
4412
4413
4414
4415
4416





67
75110_11D03A
GFTFSSYW
INQDGNEK
AREGGQWLALDY
QGISSW
GAS
QQANSFPWT




4445
4446
4447
4448
4449
4450





68
75110_12C19A
GFTFSSYW
IKEDGSDK
VREGGQWLALDY
QGISSW
GAS
QQANSFPWT




4479
4480
4481
4482
4483
4484





69
75110_12H17A
GFTFSDYW
IKEDGNEK
AREGGQWLALDY
QGISSW
GAS
QQANSFPWT




4513
4514
4515
4516
4517
4518





70
75110_12H19A
GFTFSSYW
INEDGNEK
AREGGQWLALDY
QGISSW
GAS
QQANSFPWT




4547
4548
4549
4550
4551
4552





71
75110_12K21A
GGSFSGYY
INHSGST
ARVLNYFDY
PDIANW
AAS
QQANSFPLT




4581
4582
4583
4584
4585
4586





72
75110_13C07A
GFTFSNYD
IGTAGDT
ARGAYGYYGMDV
QSVSSSY
GAS
QQYGFSPFT




4615
4616
4617
4618
4619
4620





73
75110_13C13A
GGSFSGYY
INHSGST
ARVLNFFDY
PGISNW
AAS
QQANSFPLT




4649
4650
4651
4652
4653
4654





74
75110_13P21A
GGSFSGYY
INHSGST
ARVLNYFDY
PDIANW
AAS
QQANSFPLT




4683
4684
4685
4686
4687
4688





75
75110_13P22A
GGSFSGYY
INQSGNT
ARVLNWFDY
QGISDW
AAS
QQANSFPYT




4717
4718
4719
4720
4721
4722





76
75110_14G10A
GFTFSSYS
ISSSSSYI
ARERGDDYGDYEGAFDI
QDISNY
DAS
QQYDNLPYT




4751
4752
4753
4754
4755
4756





77
75110_14H13A
GFTFSNYD
IGTAGDT
ARGGDYYYGMDV
QSVSSSY
GAS
QQFGSSPFT




4785
4786
4787
4788
4789
4790





78
75110_14116A
NGSISSYY
IYTSGST
ARDREDYYYYGMDV
HDISNY
YAS
QQYDNLPLT




4819
4820
4821
4822
4823
4824





79
75110_14N19A
GGSISRYY
ICTSENP
ARELERLNYYGMDV
QDISNY
DAS
QQYDTLPIT




4853
4854
4855
4856
4857
4858





80
75110_14P05A
GFTFSSYD
IGTAGDT
ARGGFYYYGMDV
QSVSSSY
GAS
QQSGSSPFT




4887
4888
4889
4890
4891
4892





81
75110_14P08A
GDSIRSYY
IYASGST
ARDGGVGDSLDY
QSLLDSDDGNTY
TLS
MQRIEFPFT




4921
4922
4923
4924
4925
4926





82
75110_01A07A_2
GGSIINYY
IYSSGST
AREREAYLYYGLDV
QGITNY
VTS
LQHNNYPLT




4955
4956
4957
4958
4959
4960
















TABLE 17







CD4 Antibody Sequence Summary












Heavy Chain
Light Chain























V
V %

D %
J
J %

V
V %
J
J %


Notes
Antibody
Type
Gene
Match
D Gene
Match
Gene
Match
Type
Gene
Match
Gene
Match





Sib1.1
75110_05F19A
VH
IGHV3-13
 98.3%
IGHD2-15
  100.0%
IGHJ6
 96.2%
κ
IGKV3-20
 99.3%
IGKJ3
100.0%


Sib1.2
75110_10016A
VH
IGHV3-13
 97.9%

  100.0%
IGHJ6
100.0%
κ
IGKV3-20
 97.6%
IGKJ3
100.0%


Sib1.3
75110_01K10A
VH
IGHV3-13
 97.6%
IGHD3-10
  100.0%
IGHJ6
100.0%
κ
IGKV3-20
 97.9%
IGKJ3
100.0%


Sib1.4
75110_04P06A
VH
IGHV3-13
 98.3%
IGHD3-10
  100.0%
IGHJ6
100.0%
κ
IGKV3-20
 97.9%
IGKJ3
100.0%


Sib1.5
75110_13C07A
VH
IGHV3-13
 98.3%
IGHD3-10
  100.0%
IGHJ6
100.0%
κ
IGKV3-20
 99.0%
IGKJ3
100.0%


Sib1.6
75110_01G11A
VH
IGHV3-13
 99.0%
IGHD3-16
  100.0%
IGHJ6
100.0%
κ
IGKV3-20
 95.5%
IGKJ3
100.0%


Sib1.7
75110_04F22A
VH
IGHV3-13
 99.3%
IGHD3-16
  100.0%
IGHJ6
100.0%
κ
IGKV3-20
 98.6%
IGKJ3
 97.4%


Sib1.8
75110_08H11A
VH
IGHV3-13
 99.7%
IGHD3-16
  100.0%
IGHJ6
 98.2%
κ
IGKV3-20
 99.0%
IGKJ3
100.0%


Sib1.9
75110_14H13A
VH
IGHV3-13
 98.3%
IGHD3-16
  100.0%
IGHJ6
100.0%
κ
IGKV3-20
 99.7%
IGKJ3
100.0%


Sib1.10
75110_14P05A
VH
IGHV3-13
 98.6%
IGHD3-16
  100.0%
IGHJ6
100.0%
κ
IGKV3-20
 98.6%
IGKJ3
 97.4%


Sib1.11
75110_01E08A
VH
IGHV3-13
 98.3%


IGHJ6
100.0%
κ
IGKV3-20
 99.3%
IGKJ3
100.0%


Sib1.12
75110_01J17A
VH
IGHV3-13
 97.9%


IGHJ6
 98.2%
κ
IGKV3-20
 97.9%
IGKJ3
100.0%


Sib1.13
75110_01N04A
VH
IGHV3-13
 98.6%


IGHJ6
 96.4%
κ
IGKV3-20
 98.6%
IGKJ3
100.0%


Sib1.14
75110_02I18A
VH
IGHV3-13
 99.0%


IGHJ6
100.0%
κ
IGKV3-20
 97.9%
IGKJ3
100.0%


Sib1.15
75110_05K11A
VH
IGHV3-13
 98.6%


IGHJ6
100.0%
κ
IGKV3-20
 97.6%
IGKJ3
100.0%


Sib1.16
75110_07E04A
VH
IGHV3-13
 97.9%


IGHJ6
100.0%
κ
IGKV3-20
 99.3%
IGKJ3
100.0%


Sib1.17
75110_08H06A
VH
IGHV3-13
 99.0%


IGHJ6
 98.2%
κ
IGKV3-20
 98.3%
IGKJ3
 97.4%


Sib1.18
75110_08K12A
VH
IGHV3-13
 98.6%


IGHJ6
 98.3%
κ
IGKV3-20
 98.3%
IGKJ3
100.0%


Sib1.19
75110_10L22A
VH
IGHV3-13
 99.3%


IGHJ6
 96.6%
κ
IGKV3-20
 99.7%
IGKJ3
100.0%


Sib1.20
75110_10N21A
VH
IGHV3-13
 99.3%


IGHJ6
100.0%
κ
IGKV3-20
 98.3%
IGKJ3
 97.4%



75110_05E13A
VH
IGHV3-15
 96.7%

 100.0%
IGHJ4
100.0%
κ
IGKV1-5
 98.6%
IGKJ2
100.0%



75110_04G02A
VH
IGHV3-15
 99.3%
IGHD3-10
 100.0%
IGHJ3
100.0%
κ
IGKV4-1
 96.7%
IGKJ2
100.0%



75110_05A11A
VH
IGHV3-15
 98.7%
IGHD6-19
 100.0%
IGHJ4
100.0%
κ
IGKV1-33
 98.6%
IGKJ4
 97.2%



75110_14G10A
VH
IGHV3-21
 99.3%
IGHD4-17
 100.0%
IGHJ3
100.0%
κ
IGKV1-33
100.0%
IGKJ2
100.0%



75110_04B08A
VH
IGHV3-33
 96.3%
IGHD1-1
 100.0%
IGHJ4
 97.6%
κ
IGKV1-6
 98.3%
IGKJ1
100.0%



75110_01C18A
VH
IGHV3-53
 96.2%
IGHD1-7
 100.0%
IGHJ3
100.0%
κ
IGKV1-12
 98.9%
IGKJ2
100.0%



75110_07J02A
VH
IGHV3-7
 99.7%
IGHD1-26
 100.0%
IGHJ6
100.0%
κ
IGKV1-6
 98.9%
IGKJ2
 97.4%



75110_10K21A
VH
IGHV3-7
 98.3%
IGHD3-16
 100.0%
IGHJ3
 98.0%
κ
IGKV1-6
 98.2%
IGKJ2
100.0%



75110_08A13A
VH
IGHV3-7
 98.6%
IGHD4-23
 100.0%
IGHJ6
100.0%
κ
IGKV1-6
 97.5%
IGKJ2
100.0%


Sib2.1
75110_01A06A
VH
IGHV3-7
 98.3%
IGHD6-19
 100.0%
IGHJ4
 97.6%
κ
IGKV1-12
 98.6%
IGKJ1
100.0%


Sib2.2
75110_01J09A
VH
IGHV3-7
 97.3%
IGHD6-19
 100.0%
IGHJ4
100.0%
κ
IGKV1-12
 95.4%
IGKJ1
100.0%


Sib2.3
75110_02N15A
VH
IGHV3-7
 97.6%
IGHD6-19
 100.0%
IGHJ4
 95.2%
κ
IGKV1-12
 98.2%
IGKJ1
 97.2%


Sib2.4
75110_03B16A
VH
IGHV3-7
 96.3%
IGHD6-19
 100.0%
IGHJ4
100.0%
κ
IGKV1-12
 97.9%
IGKJ1
 97.4%


Sib2.5
75110_03D16A
VH
IGHV3-7
 98.6%
IGHD6-19
 100.0%
IGHJ4
100.0%
κ
IGKV1-12
 98.2%
IGKJ1
100.0%


Sib2.6
75110_04K10A
VH
IGHV3-7
 98.6%
IGHD6-19
 100.0%
IGHJ4
100.0%
κ
IGKV1-12
 97.5%
IGKJ1
100.0%


Sib2.7
75110_07H07A
VH
IGHV3-7
 98.3%
IGHD6-19
 100.0%
IGHJ4
100.0%
κ
IGKV1-12
 98.9%
IGKJ1
 94.7%


Sib2.8
75110_09G15A
VH
IGHV3-7
 97.6%
IGHD6-19
  90.9%
IGHJ4
100.0%
κ
IGKV1-12
 97.5%
IGKJ1
100.0%


Sib2.9
75110_09N20A
VH
IGHV3-7
 98.6%
IGHD6-19
 100.0%
IGHJ4
100.0%
κ
IGKV1-12
 98.6%
IGKJ1
 97.4%


Sib2.10
75110_11D03A
VH
IGHV3-7
 98.3%
IGHD6-19
 100.0%
IGHJ4
 97.6%
κ
IGKV1-12
 98.6%
IGKJ1
100.0%


Sib2.11
75110_12C19A
VH
IGHV3-7
 98.3%
IGHD6-19
 100.0%
IGHJ4
100.0%
κ
IGKV1-12
 98.9%
IGKJ1
100.0%


Sib2.12
75110_12H17A
VH
IGHV3-7
 98.0%
IGHD6-19
 100.0%
IGHJ4
 97.6%
κ
IGKV1-12
 98.2%
IGKJ1
100.0%


Sib2.13
75110_12H19A
VH
IGHV3-7
 96.6%
IGHD6-19
 100.0%
IGHJ4
 97.6%
κ
IGKV1-12
 98.9%
IGKJ1
100.0%



75110_05L07A
VH
IGHV3-7
 98.6%
IGHD6-19
 100.0%
IGHJ4
100.0%
κ
IGKV3-20
 99.3%
IGKJ3
100.0%


Sib3.1
75110_02K11A
VH
IGHV4-31
 97.3%

 100.0%
IGHJ3
100.0%
κ
IGKV3-20
 99.0%
IGKJ3
100.0%


Sib3.2
75110_04G16A
VH
IGHV4-31
 97.7%

 100.0%
IGHJ3
100.0%
κ
IGKV3-20
 99.0%
IGKJ3
100.0%



75110_05G15A
VH
IGHV4-31
 98.3%
IGHD5-12
 100.0%
IGHJ2
100.0%
κ
IGKV3-20
100.0%
IGKJ2
100.0%



75110_13P22A
VH
IGHV4-34
 97.3%
IGHD1-1
 100.0%
IGHJ4
 97.7%
κ
IGKV1-12
 96.8%
IGKJ2
100.0%


Sib4.1
75110_12K21A
VH
IGHV4-34
 98.3%

 100.0%
IGHJ4
100.0%
κ
IGKV1-12
 97.2%
IGKJ4
 97.2%


(identical)















Sib4.1
75110_13P21A
VH
IGHV4-34
 98.3%

 100.0%
IGHJ4
100.0%
κ
IGKV1-12
 97.2%
IGKJ4
 97.2%


(identical)















Sib4.2
75110_13C13A
VH
IGHV4-34
 98.6%

 100.0%
IGHJ4
 97.9%
κ
IGKV1-12
 97.2%
IGKJ4
 97.2%


Sib5.1
75110_04P08A
VH
IGHV4-34
 96.2%

 100.0%
IGHJ5
 97.8%
κ
IGKV1-12
 98.2%
IGKJ2
100.0%


Sib5.2
75110_06D16A
VH
IGHV4-34
 99.3%

 100.0%
IGHJ5
100.0%
κ
IGKV1-12
 97.5%
IGKJ2
 97.4%



75110_03L12A
VH
IGHV4-34
 98.3%
IGHD2-21
 100.0%
IGHJ5
100.0%
κ
IGKV1-12
 98.2%
IGKJ2
 94.7%



75110_05B13A
VH
IGHV4-34
 95.9%
IGHD2-21
 100.0%
IGHJ5
100.0%
κ
IGKV1-12
 97.9%
IGKJ4
100.0%


Sib6.1
75110_01H18A
VH
IGHV4-34
 99.0%
IGHD3-10
 100.0%
IGHJ5
 97.8%
κ
IGKV1-12
 98.6%
IGKJ2
 97.4%


Sib6.2
75110_03C01A
VH
IGHV4-34
 98.6%
IGHD3-10
 100.0%
IGHJ5
 95.7%
κ
IGKV1-12
 97.2%
IGKJ2
100.0%


Sib6.3
75110_07B16A
VH
IGHV4-34
 98.6%
IGHD3-10
 100.0%
IGHJ5
 95.7%
κ
IGKV1-12
 97.9%
IGKJ2
100.0%



75110_01D24A
VH
IGHV4-34
 99.3%
IGHD3-9
 100.0%
IGHJ5
100.0%
κ
IGKV1-12
 96.8%
IGKJ2
 92.1%



75110_02I16A
VH
IGHV4-34
 96.2%


IGHJ5
100.0%
κ
IGKV1-12
 96.1%
IGKJ2
100.0%


Sib7.1
75110_02E22A
VH
IGHV4-4
 99.3%

  90.9%
IGHJ6
 98.1%
κ
IGKV1-33
 97.5%
IGKJ4
100.0%


Sib7.2
75110_04D20A
VH
IGHV4-4
 96.6%
IGHD1-1
 100.0%
IGHJ6
 96.3%
κ
IGKV1-33
 98.9%
IGKJ4
 97.4%


Sib7.3
75110_04H17A
VH
IGHV4-4
 96.2%
IGHD1-1
 100.0%
IGHJ6
100.0%
κ
IGKV1-33
 98.6%
IGKJ4
100.0%


Sib7.4
75110_06G04A
VH
IGHV4-4
 97.3%
IGHD1-1
 100.0%
IGHJ6
 98.1%
κ
IGKV1-33
 99.3%
IGKJ4
 97.4%


Sib7.5
75110_06K03A
VH
IGHV4-4
 98.0%
IGHD1-1
 100.0%
IGHJ6
100.0%
κ
IGKV1-33
 98.6%
IGKJ4
100.0%


Sib7.6
75110_06C16A
VH
IGHV4-4
 96.6%


IGHJ6
100.0%
κ
IGKV1-33
 97.9%
IGKJ4
100.0%


Sib7.7
75110_08F20A
VH
IGHV4-4
 96.6%
IGHD1-1
 100.0%
IGHJ6
 98.1%
κ
IGKV1-33
 98.2%
IGKJ5
 97.4%


Sib7.8
75110_08G08A
VH
IGHV4-4
 97.3%
IGHD1-1
 100.0%
IGHJ6
 98.1%
κ
IGKV1-33
 98.9%
IGKJ5
 97.4%


Sib7.9
75110_14N19A
VH
IGHV4-4
 97.6%
IGHD1-1
 100.0%
IGHJ6
100.0%
κ
IGKV1-33
 97.5%
IGKJ5
 97.4%


Sib7.10
75110_06E14A
VH
IGHV4-4
 98.0%
IGHD3-10
 100.0%
IGHJ6
100.0%
κ
IGKV1-33
 98.6%
IGKJ5
100.0%



75110_01A07A_1
VH
IGHV4-4
96.60%
IGHD1-26
100.00%
IGHJ6
98.10%
κ
IGKV1-33
 98.9%
IGKJ4
100.0%



75110_01A07A_2
VH
IGHV4-4
96.60%
IGHD1-26
100.00%
IGHJ6
98.10%
κ
IGKV1-17
 95.8%
IGKJ4
100.0%



75110_02E08A
VH
IGHV4-4
 97.3%
IGHD1-7
  93.3%
IGHJ3
100.0%
κ
IGKV1-17
 99.7%
IGKJ1
100.0%


Sib8.1
75110_05E05A
VH
IGHV4-4
 98.0%
IGHD3-16
 100.0%
IGHJ4
100.0%
κ
IGKV2-40
 99.7%
IGKJ3
100.0%


Sib8.2
75110_14P08A
VH
IGHV4-4
 95.9%
IGHD3-16
 100.0%
IGHJ4
100.0%
κ
IGKV2-40
100.0%
IGKJ3
100.0%


Sib9.1
75110_03I23A
VH
IGHV4-4
 98.3%
IGHD5-18
 100.0%
IGHJ3
 98.0%
κ
IGKV1-33
 98.9%
IGKJ4
100.0%


Sib9.2
75110_07N04A
VH
IGHV4-4
 97.3%
IGHD5-18
 100.0%
IGHJ3
 98.0%
κ
IGKV1-33
 99.3%
IGKJ4
100.0%



75110_07J24A
VH
IGHV4-4
 96.9%


IGHJ3
100.0%
κ
IGKV2-40
 98.3%
IGKJ3
100.0%


Sib10.1
75110_08D24A
VH
IGHV4-4
 97.3%


IGHJ6
100.0%
κ
IGKV1-33
 98.9%
IGKJ5
100.0%


Sib10.2
75110_08M20A
VH
IGHV4-4
 99.0%


IGHJ6
100.0%
κ
IGKV1-33
 98.2%
IGKJ5
100.0%


Sib10.3
75110_14I16A
VH
IGHV4-4
 98.3%


IGHJ6
 98.3%
κ
IGKV1-33
 97.5%
IGKJ4
100.0%



75110_03I08A
VH
IGHV4-59
 99.7%
IGHD6-19
 100.0%
IGHJ6
 98.0%
κ
IGKV3-20
 98.3%
IGKJ5
100.0%



75110_01L08A
VH
IGHV4-59
 97.6%
IGHD6-19
  92.9%
IGHJ6
100.0%
κ
IGKV1-33
 99.6%
IGKJ4
100.0%
















TABLE 18







Non-Clonal Supernantant Screening: FACS Analysis and Epitope Binning



























ELISA Binning




























Ibalizumab













ELISA
















Primary Screens
Confirmation Screening-FACS



Binning






















SKW3
SKW3





Experiment-




















WT
WT
PBMCs,
PBMCs,
SKW3 FACS Binning
100 ng/mL






















anti-
anti-hu
anti-
anti-
OKT4
RPA-T4-
OKT4a anti-
huCD4-HIS-




SKW3
SKW3
mFc
Kappa
mFc
mFc
A488
PE−
hu A647
anti-HIS HRP




WT vs
WT vs
647,
FITC,
647
647
Background-
Dazzle 594
Secondary
detection




KO
KO
gMFI
gMFI
CD4+
CD4+
2163
Background-
Background-
Background-




anti-
anti-
(Bkrd
(Bkrd
gate-
Percent
Max
783
5000
45




mFc-
hKappa-
gMFI =
gMFI =
RL1
Bound of
Binding-
Max Binding-
Max Binding-
Max Binding-
BIN


Hybridoma ID
647
FITC
3300)
2500)
BInding
Viable
8200
15000
35000
3000000
#





















75110_01A07A
6.0
1.3
23745
4828
288876
35
6515
8738
42954
426129
Ibalizumab


75110_01L08A
4.3
2.6
18705
5516
199655
27
9752
19766
9034
58214
Ibalizumab


75110_02I18A
4.2
2.2
16461
5374
274874
29
9228
4414
44772
291057
Ibalizumab


75110_03I08A
7.6
2.2
27994
6123
338421
32
11169
3351
24751
20349
Ibalizumab


75110_04G02A
6.6
1.5
12037
4059
178405
27
9326
12125
22471
45
Ibalizumab


75110_05A11A
3.4
1.8
24449
6615
246769
26
8161
17155
34999
45
Ibalizumab


75110_05E13A
5.8
1.9
45600
8050
230515
26
9329
16525
36438
45
Ibalizumab


75110_05F19A
10.6
2.8
42224
8509
280604
31
8923
15862
29952
45
Ibalizumab


75110_07J24A
6.2
1.8
30855
5826
234133
33
7727
8463
33773
215326
Ibalizumab


75110_08A13A
2.7
1.0
9181
3145
258187
29
7977
13340
42022
230020
Ibalizumab


75110_01C18A
14.7
3.7
34887
6533
308040
31
9486
16530
36249
1783061
No Bin


75110_02E22A
4.7
1.6
17328
4279
275723
31
8476
15295
41888
1861052
No Bin


75110_02K11A
10.3
3.3
24783
6655
296309
29
8729
15815
32191
1992168
No Bin


75110_03I23A
4.1
1.9
13809
5145
241454
28
9919
14048
15858
1258599
No Bin


75110_04D20A
4.5
2.3
21903
6791
174317
28
7369
17146
29209
2105763
No Bin


75110_04H17A
2.9
1.6
27204
7426
301981
30
9439
16792
33959
1893266
No Bin


75110_05E05A
9.4
3.2
38765
8324
227125
28
9102
16458
35536
1640077
No Bin


75110_05G15A
2.8
1.5
28623
5996
146777
32
8077
15844
42348
1702809
No Bin


75110_06C16A
5
1.9
12105
4655
296555
28
8237
15634
36808
1353545
No Bin


75110_06E14A
9.8
3.0
33848
8917
284855
30
9063
16399
31319
1767802
No Bin


75110_06G04A
9.3
3.3
33736
8483
240424
30
9314
16585
30812
1959954
No Bin


75110_06K03A
7.5
2.7
33550
8636
296312
32
9144
15793
33247
1645729
No Bin


75110_07J02A
2.3
1.3
13428
3985
89171
27
8052
15914
38005
1982560
No Bin


75110_07N04A
7.8
2.8
30416
6228
343981
30
9014
15544
36147
1655336
No Bin


75110_08D24A
4.1
1.1
20074
3573
277834
30
7930
14626
42513
886728
No Bin


75110_08F20A
3.1
1.7
31494
6169
253115
32
7408
15489
44792
1413451
No Bin


75110_08G08A
5.7
2.4
19412
5845
313823
30
8890
16154
38446
1692071
No Bin


75110_08K12A
4.7
1.7
16592
5299
276135
29
8657
16045
39153
1980865
No Bin


75110_08M20
7.2
3.2
31430
8253
319755
33
9018
15980
34986
1654771
No Bin


75110_08M20A
8.8
2.7
30733
7786
318987
30
9132
16585
37201
908769
No Bin


75110_10O16A
2.4
1.3
5461
3161
72092
23
8258
15348
34850
2374776
No Bin


75110_14G10A
2.2
1.1
8911
3413
141601
32
8716
10141
41809
1208865
No Bin


75110_14116A
2.1
1.4
6820
3554
195816
23
8010
15315
32994
2258355
No Bin


75110_14N19A
14.9
3.8
28628
7639
276795
29
9082
16644
29723
1283466
No Bin


75110_14P08A
6.7
2.2
20284
5583
291529
30
9101
16418
38366
2202970
No Bin


75110_01E08A
5.9
2.2
22891
6338
302344
29
3333
14425
43278
1840141
OKT4


75110_02N15A
4.9
2.1
15881
5004
249701
27
3025
14245
42862
1980299
OKT4


75110_03B16A
6.2
2.2
31230
6802
240617
30
2473
15076
45128
1466575
OKT4


75110_03D16A
6.5
2.8
36046
7596
318619
31
2278
12296
35873
662928
OKT4


75110_04B08A
6.7
2.3
22596
6157
274235
29
3166
14918
43367
1945825
OKT4


75110_04K10A
5
1.5
36741
6710
345723
33
2765
9805
43099
1126353
OKT4


75110_05L07A
3.9
1.5
16332
5130
180625
29
3125
15871
37399
2570319
OKT4


75110_07H07A
5.7
2.3
34268
8512
233585
27
2065
14937
39400
2111980
OKT4


75110_09G15A
4.8
2.0
22267
5806
304141
28
2989
14814
44604
1992168
OKT4


75110_09N20A
5.4
2.2
24812
5876
287063
33
2702
14679
46618
1761585
OKT4


75110_10L22A
3.4
2.1
27585
7020
283145
31
2849
14992
45900
1880832
OKT4


75110_11D03A
2.6
1.0
21089
3995
190309
29
4178
13148
43723
1628209
OKT4


75110_12H17A
4.0
2.0
17986
5355
263669
29
4018
14813
41996
2203535
OKT4


75110_12H19A
5.2
2.4
22813
6548
243836
27
2625
14638
34377
1736718
OKT4


75110_01A06A
7.5
2.4
32302
5927
321177
31
2135
14664
43658
1260294
OKT4


75110_01J09A
7.5
2.4
32302
5927
321177
31
2135
14664
43658
1260294
OKT4


75110_02E08A
8.4
3.1
30910
7262
316961
31
3317
13511
41534
334574
OKT4/













Ibalizumab


75110_03C01A
8
2.4
18720
5915
265590
28
9511
19208
6982
865252
OKT4a


75110_03L12A
4.2
2.5
27321
8013
229292
28
9752
20663
5715
885033
OKT4a


75110_04P08A
8.4
3
25343
7415
259647
28
9759
19903
6063
1569433
OKT4a


75110_05B13A
3.1
2.4
26022
7308
227873
27
9667
20253
5336
1031973
OKT4a


75110_06D16A
4
2.5
41343
8670
215613
29
9980
21306
5795
1267076
OKT4a


75110_07B16A
11.4
3.0
30754
7224
273723
29
9283
20578
5325
1307767
OKT4a


75110_12C19A
7.2
2.3
29283
6850
340556
31
9584
11856
7138
1507831
OKT4a


75110_12K21A
6.6
2.8
24953
5624
335494
30
10008
10885
8238
1412886
OKT4a


75110_13C13A
6.8
3.1
23885
7239
99619
6
9763
20793
5495
1173261
OKT4a


75110_13P21A
5.8
2.4
30903
7577
273616
31
9419
11860
6868
677622
OKT4a


75110_13P22A
6.4
2.8
18171
5906
215437
27
9367
19027
6216
1160827
OKT4a


75110_14P05A
4.6
2.8
24046
7515
186984
27
9340
20281
6113
709835
OKT4a


75110_01D24A
6.8
2.5
24970
5516
257352
31
11113
15174
5320
20349
OKT4a/













Ibalizumab


75110_04G16A
6.3
2.3
32522
6830
254923
32
9641
13543
6741
52562
OKT4a/













Ibalizumab


75110_01G11A
3.4
2
19228
4998
243602
30
10116
2159
30137
495077
RPA-14


75110_01J17A
4.3
2.1
31576
5780
280451
32
10014
1951
37668
755048
RPA-T4


75110_01K10A
4.6
2.2
24264
5945
282834
30
10786
1513
29991
890119
RPA-14


75110_01N04A
3.7
1.9
27986
5635
209561
33
9721
2243
38092
1041580
RPA-14


75110_02I16A
3.0
1.7
19398
5736
217654
29
9808
2593
30654
822866
RPA-14


75110_04F22A
3.6
1.8
26941
5583
286484
32
9945
2293
40217
748266
RPA-14


75110_04P06A
3.9
1.6
24548
5601
292218
31
10076
2190
37441
1219603
RPA-14


75110_05K11A
4
1.8
35890
6704
266773
31
9727
2193
37616
1176652
RPA-14


75110_07E04A
2.9
1.8
21985
6360
206329
30
9944
2425
31343
1730502
RPA-14


75110_08H06A
3.0
1.6
22983
6272
224764
30
10404
2477
29907
1420798
RPA-T4


75110_08H11A
2.8
1.6
18557
5232
245967
31
9773
3091
35984
868643
RPA-14


75110_10K21A
2.6
1.7
19178
5846
223996
32
9978
2591
34061
292752
RPA-14


75110_10N21A
3.1
1.4
13042
4064
178782
33
9087
6881
40125
1575650
RPA-14


75110_13C07A
3.1
1.6
23131
5725
302782
35
9593
2508
38946
1703940
RPA-14


75110_01H18A
3.6
1.6
19013
4930
263045
32
9844
2826
37208
384872
RPA-14/













Ibalizumab


75110_14H13A
4.8
1.9
21981
6013
292358
29
12694
1664
14284
2264
RPA-14/













Ibalizumab


75110_06L01A
9.3
2.9
40372
9916
283047
33
9095
16482
33465
406913
No Bin


75110_07G23A
11.6
2.7
31612
7302
301136
31
9270
15294
37135
2176973
No Bin


75110_09I11A
4.9
2.0
25081
5432
141191
23
9809
3520
38995
1070403
No Bin


75110_09L24A
4.9
1.1
10029
2979
80840
25
6389
14526
37420
2291699
No Bin


75110_02L13A
7.2
2.5
24212
7610
266143
28
9692
19862
6092
1016148
OKT4a


75110_11F17A
5.7
2.8
28445
8093
255713
28
9399
20938
6206
762960
OKT4a


75110_09K15A
2.8
1.3
10726
3934
172113
28
8971
7526
37018
934201
RPA-14
















TABLE 19







Nonclonal Supernatant Screening: Off-rate Screening














Full
Antibody Loading


kon
kdis


Hybridoma ID
R{circumflex over ( )}2
(nm, estimated)
Response
KD (M)
(1/Ms)
(1/s)
















75110_01A07A
0.97
1.6
0.24
   6.0E−09
   1.4E+05
   8.1E−04


75110_01L08A
0.98
0.9
0.09
   4.1E−09
   9.1E+04
   3.7E−04


75110_02I18A
0.84
0.9
0.16
   9.0E−09
   3.7E+05
   3.3E−03


75110_03I08A
0.96
1
0.07
 <1.0E−12
   3.7E+04
 <1.0E−07


75110_04G02A
0.97
1
0.21
   7.6E−10
   2.2E+05
   1.7E−04


75110_05A11A
0.97
0.8
0.15
   3.2E−09
   1.7E+05
   5.5E−04


75110_05E13A
0.99
1
0.33
   7.4E−09
   1.6E+05
   1.2E−03


75110_05F19A
0.99
0.8
0.18
   3.2E−11
   1.4E+05
   4.4E−06


75110_07J24A
0.99
1.2
0.14
 <1.0E−12
   7.7E+04
 <1.0E−07


75110_08A13A
0.90
1.7
0.35
   4.4E−09
   2.3E+05
   1.0E−03


75110_01C18A
1.00
1
0.25
   1.6E−08
   8.6E+04
   1.3E−03


75110_02E22A
0.95
1
0.18
   2.0E−08
   2.1E+05
   4.2E−03


75110_02K11A
0.96
0.8
0.14
   1.7E−08
   1.3E+05
   2.2E−03


75110_03I23A
0.97
0.8
0.18
   8.6E−09
   1.4E+05
   1.2E−03


75110_04D20A
1.00
0.7
0.20
   8.8E−10
   1.5E+05
   1.3E−04


75110_04H17A
0.99
0.7
0.16
   9.0E−09
   1.1E+05
   9.7E−04


75110_05E05A
0.99
1
0.24
   9.5E−10
   1.4E+05
   1.3E−04


75110_05G15A
0.99
0.9
0.24
 <1.0E−12
   7.8E+04
 <1.0E−07


75110_06C16A
0.74
1.7
0.07
   9.7E−09
   2.5E+05
   2.4E−03


75110_06E14A
0.97
0.9
0.12
   1.2E−08
   1.7E+05
   2.0E−03


75110_06G04A
0.99
0.8
0.12
   1.4E−08
   7.5E+04
   1.0E−03


75110_06K03A
0.83
0.7
0.14
   6.8E−09
   2.8E+05
   1.9E−03


75110_07J02A
0.99
0.7
0.1303
  5.60E−10
  6.84E+04
  3.83E−05


75110_07N04A
0.90
0.4
0.10
 <1.0E−12
   1.4E+05
 <1.0E−07


75110_08D24A
0.99
1.5
0.21
   3.4E−08
   1.7E+05
   6.0E−03


75110_08F20A
0.99
1.1
0.32
   1.9E−09
   1.4E+05
   2.6E−04


75110_08G08A
0.82
0.8
0.13
   3.4E−09
   2.8E+05
   9.6E−04


75110_08K12A
0.73
0.8
0.11
   4.5E−09
   7.0E+05
   3.1E−03


75110_08M20
0.99
1.1
0.11
   3.9E−08
   4.9E+04
   1.9E−03


75110_08M20A
0.93
1
0.19
   3.6E−09
   1.5E+05
   5.3E−04


75110_10O16A
0.95
0.7
0.0936
 <1.0E−12
  6.48E+04
 <1.0E−07


75110_14G10A
0.96
0.05
0.0363
 <1.0E−12
  7.88E+04
 <1.0E−07


75110_14I16A
0.74
0.8
0.0852
 <1.0E−12
  4.27E+04
 <1.0E−07


75110_14N19A
0.99
0.8
0.1049
  1.92E−08
  1.43E+05
  2.74E−03


75110_14P08A
0.90
0.5
0.0968
  7.47E−09
  1.79E+05
  1.34E−03


75110_01E08A
0.86
0.9
0.10
   1.0E−08
   1.4E+05
   1.4E−03


75110_02N15A
0.96
0.8
0.16
   6.7E−09
   1.0E+05
   6.9E−04


75110_03B16A
0.98
1.2
0.19
   1.5E−08
   1.8E+05
   2.7E−03


75110_03D16A
0.93
0.7
0.25
   6.0E−09
   2.2E+05
   1.3E−03


75110_04B08A
0.83
0.5
0.14
   5.2E−09
   2.3E+05
   1.2E−03


75110_04K10A
0.92
1
0.23
   6.3E−09
   2.9E+05
   1.8E−03


75110_05L07A
0.95
1.3
0.12
   1.3E−08
   1.0E+05
   1.4E−03


75110_07H07A
0.99
0.8
0.20
   3.1E−09
   1.1E+05
   3.5E−04


75110_09G15A
0.95
1
0.10
   2.9E−07
   3.7E+04
   1.1E−02


75110_09N20A
0.95
0.7
0.13
   1.5E−08
   1.3E+05
   1.9E−03


75110_10L22A
0.9962
0.9
0.1127
  1.17E−07
  5.57E+04
  6.50E−03


75110_11D03A
0.9899
0.95
0.1774
  4.67E−09
  1.12E+05
  5.24E−04


75110_12H17A
0.80
0.9
0.09
   9.6E−09
   3.3E+05
   3.2E−03


75110_12H19A
0.90
0.05
0.09
   4.2E−09
   2.9E+05
   1.2E−03


75110_01A06A
1.00
1.3
0.28
   1.1E−08
   1.2E+05
   1.3E−03


75110_01J09A
1.00
1.3
0.28
   1.1E−08
   1.2E+05
   1.3E−03


75110_02E08A
0.45
0.7
0.08
   1.5E−09
   3.3E+05
   5.1E−04


75110_03C01A
0.96
0.25
0.09
 <1.0E−12
   1.5E+05
 <1.0E−07


75110_03L12A
0.99
0.8
0.21
   2.8E−09
   1.7E+05
   4.8E−04


75110_04P08A
0.99
0.6
0.17
   1.8E−09
   1.2E+05
   2.2E−04


75110_05B13A
0.64
1.2
0.03
 <1.0E−12
   2.0E+05
 <1.0E−07


75110_06D16A
0.94
1.1
0.09
   2.5E−09
   1.9E+05
   4.7E−04


75110_07B16A
0.99
0.7
0.21
   7.9E−10
   1.6E+05
   1.3E−04


75110_12C19A
0.99
0.6
0.1056
  6.27E−10
  1.54E+05
  9.63E−05


75110_12K21A
0.86
1.5
0.26
   3.0E−09
   2.0E+05
   6.0E−04


75110_13C13A
0.99
0.9
0.19
   3.2E−09
   1.6E+05
   5.1E−04


75110_13P21A
0.98
1
0.1201
  2.04E−09
  1.54E+05
  3.15E−04


75110_13P22A
0.99
0.7
0.24
   6.8E−10
   1.9E+05
   1.3E−04


75110_14P05A
1.00
1
0.1491
  1.23E−08
  1.50E+05
  1.85E−03


75110_01D24A
0.99
1.3
0.26
   1.1E−09
   1.1E+05
   1.3E−04


75110_04G16A
0.99
1.6
0.15
   9.5E−10
   7.4E+04
   7.1E−05


75110_01G11A
0.94
0.95
0.04
   5.3E−09
   4.7E+04
   2.5E−04


75110_01J17A
0.95
0.9
0.06
 <1.0E−12
   3.7E+04
 <1.0E−07


75110_01K10A
0.89
1
0.03
   3.4E−07
   1.2E+03
   4.2E−04


75110_01N04A
0.99
1.2
0.06
   2.2E−09
   2.2E+04
   4.8E−05


75110_02I16A
0.86
0.8
0.0373
  3.90E−09
  3.08E+05
  1.20E−03


75110_04F22A
0.87
0.8
0.05
 <1.0E−12
   1.5E+04
 <1.0E−07


75110_04P06A
0.86
0.8
0.06
 <1.0E−12
   1.2E+04
 <1.0E−07


75110_05K11A
0.89
0.8
0.05
 <1.0E−12
   1.2E+04
 <1.0E−07


75110_07E04A
0.66
1
0.01
   1.1E−05
   1.2E+03
   1.3E−02


75110_08H06A
0.82
0.7
0.06
 <1.0E−12
   1.2E+05
 <1.0E−07


75110_08H11A
0.85
1
0.08
   2.9E−09
   2.3E+05
   6.5E−04


75110_10K21A
0.94
0.8
0.0687
  2.66E−09
  1.36E+05
  3.62E−04


75110_10N21A
0.90
0.7
0.0658
  8.73E−10
  1.52E+05
  1.33E−04


75110_13C07A
0.77
0.5
0.0171
  8.40E−08
  2.17E+05
  1.82E−02


75110_01H18A
0.82
0.7
0.0657
  9.02E−10
  1.65E+05
  1.48E−04


75110_14H13A
0.98
1
0.14
 <1.0E−12
   1.0E+05
 <1.0E−07


75110_06L01A
0.99
1
0.22
 <1.0E−12
   1.7E+05
 <1.0E−07


75110_07G23A
0.88
0.9
0.07
   1.4E−09
   1.9E+05
   2.6E−04


75110_09I11A
0.19
0.9
0.04
 <1.0E−12
   3.4E+05
 <1.0E−07


75110_09L24A
0.93
0.8
0.0955
 <1.0E−12
  1.30E+05
 <1.0E−07


75110_02L13A
0.98
1
0.08
   1.8E−09
   1.5E+05
   2.6E−04


75110_11F17A
0.98
0.7
0.20
   7.0E−10
   1.9E+05
   1.3E−04


75110_09K15A
0.94
0.7
0.03
 <1.0E−12
   4.8E+01
 <1.0E−07
















TABLE 20







Clonal Purified Data: Human CD4 Octet Kinetic Characterization













Re-
Full





Hybridoma ID
sponse
R{circumflex over ( )}2
KD (M)
kdis(1/s)
kon(1/Ms)















75110_01A06A
0.36
0.97
1.4E−08
1.4E−03
1.0E+05


75110_01A07A
0.25
0.99
1.8E−08
1.2E−03
6.8E+04


75110_01C18A
0.13
0.97
2.4E−08
4.7E−03
2.0E+05


75110_01D24A
0.27
0.97
1.3E−08
1.7E−03
1.3E+05


75110_01E08A
0.14
0.98
2.6E−10
2.0E−05
7.7E+04


75110_01G11A
0.11
0.99
1.7E−09
7.2E−05
4.2E+04


75110_01H18A
0.23
0.99
1.6E−08
1.6E−03
9.9E+04


75110_01J09A
0.12
0.99
1.3E−07
4.8E−03
3.7E+04


75110_01J17A
0.09
0.99
2.8E−09
1.2E−04
4.3E+04


75110_01K10A
0.05
0.88
<1.0E−12  
<1.0E−07  
2.3E+04


75110_01L08A
0.19
0.77
4.1E−09
1.6E−03
3.9E+05


75110_01N04A
0.08
0.98
2.1E−09
6.1E−05
2.8E+04


75110_02E08A
0.11
0.77
2.2E−09
6.1E−04
2.8E+05


75110_02E22A
0.16
0.99
5.0E−08
3.1E−03
6.3E+04


75110_02I16A
0.22
0.97
3.5E−09
4.0E−04
1.2E+05


75110_02I18A
0.05
0.96
6.6E−08
8.6E−05
1.3E+03


75110_02K11A
0.11
0.95
1.9E−08
1.4E−03
7.4E+04


75110_02N15A
0.25
0.92
1.1E−08
1.7E−03
1.6E+05


75110_03B16A
0.15
0.97
2.6E−08
3.7E−03
1.4E+05


75110_03C01A
0.23
0.92
3.0E−09
4.0E−04
1.4E+05


75110_03D16A
0.05
0.84
1.0E−08
8.0E−04
7.8E+04


75110_03I08A
0.14
0.93
8.8E−09
1.1E−03
1.3E+05


75110_03I23A
0.18
0.95
<1.0E−12  
<1.0E−07  
8.0E+04


75110_03L12A
0.22
0.95
5.5E−09
7.6E−04
1.4E+05


75110_04B08A
0.25
0.96
1.7E−08
3.7E−03
2.2E+05


75110_04D20A
0.14
0.94
8.9E−09
8.0E−04
9.0E+04


75110_04F22A
0.05
0.96
5.9E−09
2.1E−04
3.5E+04


75110_04G02A
0.17
0.99
1.6E−08
1.5E−03
9.0E+04


75110_04G16A
0.23
0.96
5.3E−09
4.7E−04
8.9E+04


75110_04H17A
0.15
0.96
2.5E−10
1.8E−05
7.3E+04


75110_04K10A
0.10
1.00
1.1E−07
4.2E−03
3.9E+04


75110_04P06A
0.07
0.96
<1.0E−12  
<1.0E−07  
2.4E+04


75110_04P08A
0.23
0.98
3.6E−09
5.0E−04
1.4E+05


75110_05A11A
0.27
0.98
1.8E−08
1.8E−03
9.7E+04


75110_05B13A
0.28
0.96
5.4E−09
5.8E−04
1.1E+05


75110_05E05A
0.18
0.98
<1.0E−12  
<1.0E-07  
3.4E+04


75110_05E13A
0.37
0.97
2.2E−09
2.2E−04
1.0E+05


75110_05F19A
0.05
0.94
<1.0E−12  
<1.0E−07  
1.9E+04


75110_05G15A
0.09
0.91
1.3E−08
2.2E−03
1.7E+05


75110_05K11A
0.04
0.94
<1.0E−12  
<1.0E−07  
3.6E+04


75110_05L07A
0.28
1.00
1.5E−08
1.6E−03
1.1E+05


75110_06C16A
0.15
0.96
1.6E−08
1.2E−03
7.5E+04


75110_06D16A
0.25
0.98
2.8E−09
2.8E−04
1.0E+05


75110_06E14A
0.11
0.97
1.4E−08
2.6E−04
1.8E+04


75110_06G04A
0.07
0.83
6.0E−09
1.5E−03
2.5E+05


75110_06K03A
0.11
0.97
2.2E−09
3.6E−05
1.6E+04


75110_07B16A
0.24
0.93
3.0E−09
4.3E−04
1.4E+05


75110_07E04A
0.07
0.97
<1.0E−12  
<1.0E−07  
3.5E+04


75110_07H07A
0.16
0.89
9.4E−09
1.2E−03
1.3E+05


75110_07J02A
0.10
0.92
1.4E−08
2.2E−03
1.6E+05


75110_07J24A
0.19
0.96
7.1E−09
6.0E−04
8.5E+04


75110_07N04A
0.20
0.96
<1.0E−12  
<1.0E−07  
8.4E+04


75110_08A13A
0.12
0.94
6.6E−09
7.8E−04
1.2E+05


75110_08D24A
0.11
0.97
2.2E−08
2.7E−04
1.2E+04


75110_08F20A
0.22
0.99
8.4E−09
1.4E−03
1.7E+05


75110_08G08A
0.15
0.99
2.0E−08
3.5E−03
1.8E+05


75110_08H06A
0.04
0.97
1.1E−08
4.3E−04
3.9E+04


75110_08H11A
0.04
0.95
2.6E−08
3.6E−05
1.4E+03


75110_08K12A
0.05
0.98
2.2E−07
2.2E−04
1.0E+03


75110_08M20A
0.16
0.99
9.2E−09
9.1E−04
9.9E+04


75110_09G15A
0.21
0.99
4.8E−08
4.0E−03
8.5E+04


75110_09N20A
0.09
0.96
5.3E−08
4.5E−03
8.6E+04


75110_10K21A
0.20
0.98
3.1E−09
4.9E−04
1.6E+05


75110_10L22A
0.03
0.64
1.2E−08
4.5E−04
3.7E+04


75110_10N21A
0.09
0.98
5.9E−10
3.2E−05
5.5E+04


75110_10O16A
0.08
0.91
2.4E−09
3.5E−04
1.4E+05


75110_11D03A
0.09
0.68
3.2E−09
1.3E−03
4.2E+05


75110_12C19A
0.08
0.81
5.0E−09
1.5E−03
2.9E+05


75110_12H17A
0.19
0.96
2.6E−08
3.3E−03
1.2E+05


75110_12H19A
0.25
0.95
1.3E−08
2.2E−03
1.7E+05


75110_12K21A
0.22
0.97
1.8E−09
2.1E−04
1.1E+05


75110_13C07A
0.11
0.97
1.7E−09
1.6E−04
9.2E+04


75110_13C13A
0.21
0.96
1.1E−08
1.3E−03
1.2E+05


75110_13P21A
0.17
0.95
3.0E−09
2.9E−04
9.5E+04


75110_13P22A
0.16
0.97
1.4E−08
1.2E−03
8.6E+04


75110_14G10A
0.19
0.88
3.8E−10
1.9E−04
5.0E+05


75110_14H13A
0.08
0.99
2.1E−09
1.1E−04
5.4E+04


75110_14I16A
0.14
0.98
1.0E−08
1.7E−03
1.6E+05


75110_14N19A
0.17
0.99
1.1E−08
1.4E−03
1.3E+05


75110_14P05A
0.05
0.91
<1.0E−12  
<1.0E−07  
9.5E+04


75110_14P08A
0.17
0.99
3.3E−10
3.2E−05
9.6E+04
















TABLE 21







Clonal Purified Data: Rhesus CD4 Octet Kinetic Characterization














Full

kdis
kon


Hybridoma ID
Response
R{circumflex over ( )}2
KD (M)
(1/s)
(1/Ms)





75110_01A06A
0.39
0.95
7.8E−09
1.0E−03
1.3E+05


75110_01A07A
0.26
0.99
2.6E−08
1.9E−03
7.2E+04


75110_01C18A
NB
NB
NB
NB
NB


75110_01D24A
0.08
0.97
3.4E−07
6.4E−02
1.9E+05


75110_01E08A
0.10
0.92
9.8E−10
1.4E−04
1.4E+05


75110_01G11A
0.03
0.90
6.4E−08
1.8E−03
2.8E+04


75110_01H18A
0.11
0.99
1.3E−07
1.7E−02
1.3E+05


75110_01J09A
0.17
0.98
7.0E−08
3.2E−03
4.6E+04


75110_01J17A
0.05
0.91
2.2E−08
1.7E−03
7.9E+04


75110_01K10A
NB
NB
NB
NB
NB


75110_01L08A
0.06
0.92
8.1E−09
1.1E−03
1.4E+05


75110_01N04A
0.02
0.78
3.5E−11
6.1E−03
1.7E+08


75110_02E08A
0.04
0.77
1.2E−08
9.1E−04
7.9E+04


75110_02E22A
0.15
0.99
5.1E−08
4.4E−03
8.7E+04


75110_02I16A
0.14
0.97
3.7E−08
9.2E−03
2.5E+05


75110_02I18A
NB
NB
NB
NB
NB


75110_02K11A
0.13
0.97
2.6E−08
1.5E−03
5.9E+04


75110_02N15A
0.29
0.96
1.4E-08
2.6E−03
1.9E+05


75110_03B16A
0.19
0.98
2.3E−08
4.0E−03
1.7E+05


75110_03C01A
0.18
0.88
9.8E−09
2.7E−03
2.8E+05


75110_03D16A
0.10
0.91
1.2E−08
2.0E−03
1.6E+05


75110_03I08A
0.04
0.85
6.1E−09
6.1E−04
1.0E+05


75110_03I23A
NB
NB
NB
NB
NB


75110_03L12A
0.08
0.98
7.2E−08
1.6E−02
2.2E+05


75110_04B08A
0.26
0.97
1.8E−08
4.8E−03
2.7E+05


75110_04D20A
0.13
0.97
1.2E−08
1.7E−03
1.4E+05


75110_04F22A
0.04
0.86
7.2E−09
1.1E−03
1.5E+05


75110_04G02A
NB
NB
NB
NB
NB


75110_04G16A
0.27
0.98
2.4E−09
2.2E−04
9.2E+04


75110_04H17A
0.18
0.97
1.7E−09
2.0E−04
1.2E+05


75110_04K10A
0.17
0.99
4.8E−08
3.2E−03
6.7E+04


75110_04P06A
NB
NB
NB
NB
NB


75110_04P08A
0.12
0.99
6.0E−08
9.1E−03
1.5E+05


75110_05A11A
NB
NB
NB
NB
NB


75110_05B13A
0.14
0.80
4.7E−09
2.0E−03
4.2E+05


75110_05E05A
0.06
0.92
2.3E−09
4.9E−05
2.1E+04


75110_05E13A
0.03
0.81
6.7E−09
7.9E−03
1.2E+06


75110_05F19A
NB
NB
NB
NB
NB


75110_05G15A
NB
NB
NB
NB
NB


75110_05K11A
0.01
0.46
7.8E−09
1.1E−03
1.4E+05


75110_05L07A
0.31
1.00
7.6E−09
1.1E−03
1.5E+05


75110_06C16A
0.15
0.97
2.7E−08
2.0E−03
7.3E+04


75110_06D16A
0.09
0.93
2.4E−07
2.2E−02
9.1E+04


75110_06E14A
0.10
0.96
2.3E−07
6.9E−04
3.0E+03


75110_06G04A
0.05
0.69
2.1E−09
1.1E−03
5.1E+05


75110_06K03A
0.13
0.97
7.8E−09
3.5E−04
4.5E+04


75110_07B16A
0.17
0.92
1.3E−08
3.3E−03
2.5E+05


75110_07E04A
0.02
0.78
2.6E−09
4.2E−04
1.6E+05


75110_07H07A
0.15
0.98
3.2E−08
3.0E−03
9.4E+04


75110_07J02A
0.14
0.95
1.8E−08
2.8E−03
1.5E+05


75110_07J24A
NB
NB
NB
NB
NB


75110_07N04A
0.03
0.83
<1.0E−12  
<1.0E−07  
1.3E+04


75110_08A13A
0.15
0.96
5.1E−09
9.8E−04
1.9E+05


75110_08D24A
0.05
0.75
5.3E−08
1.7E−03
3.2E+04


75110_08F20A
0.22
0.98
1.1E−08
2.6E−03
2.3E+05


75110_08G08A
0.15
0.96
1.9E−08
4.1E−03
2.2E+05


75110_08H06A
NB
NB
NB
NB
NB


75110_08H11A
NB
NB
NB
NB
NB


75110_08K12A
0.01
0.63
9.4E−08
5.3E−03
5.7E+04


75110_08M20A
0.17
0.99
1.7E−08
2.2E−03
1.3E+05


75110_09G15A
0.27
0.99
3.6E−08
3.0E−03
8.4E+04


75110_09N20A
0.14
0.99
4.4E−08
4.0E−03
9.2E+04


75110_10K21A
0.23
0.99
2.1E−09
3.3E−04
1.6E+05


75110_10L22A
0.02
0.54
5.5E−09
7.5E−04
1.4E+05


75110_10N21A
0.07
0.88
8.2E−09
1.0E−03
1.3E+05


75110_10O16A
0.04
0.85
3.1E−09
7.5E−04
2.4E+05


75110_11D03A
0.11
0.73
3.5E−09
1.8E−03
5.3E+05


75110_12C19A
0.10
0.90
1.6E−08
3.8E−03
2.4E+05


75110_12H17A
0.23
0.97
2.2E−08
3.2E−03
1.5E+05


75110_12H19A
0.28
0.97
1.4E−08
2.6E−03
1.9E+05


75110_12K21A
0.16
0.94
2.1E−08
5.6E−03
2.7E+05


75110_13C07A
0.05
0.79
3.9E−09
8.5E−04
2.2E+05


75110_13C13A
0.09
0.79
8.3E−09
4.6E−03
5.5E+05


75110_13P21A
0.11
0.99
7.5E−08
1.3E−02
1.7E+05


75110_13P22A
0.01
0.60
8.8E−07
7.2E−02
8.1E+04


75110_14G10A
NB
NB
NB
NB
NB


75110_14H13A
NB
NB
NB
NB
NB


75110_14I16A
0.13
0.98
1.4E−08
2.7E−03
1.9E+05


75110_14N19A
0.17
0.99
1.4E−08
2.1E−03
1.5E+05


75110_14P05A
0.02
0.69
<1.0E−12  
<1.0E−07  
9.3E+04


75110_14P08A
0.06
0.94
8.8E−09
6.6E−04
7.5E+04
















TABLE 22







Clonal Supernatant PBMC Binding & Purification Data Summary










Clonal Supernatant PBMC
Purfication



FACS Binding Data
Data Summary

















% CD4
gMFI of

Conc.
Vol.
Amt.
%
%
%


Hybridoma ID
Stain
CD4+
Lot No.
(mg/ml)
(mg/ml)
(μg)
HMW
Main
LMW



















75110_01A06A
33.7
115075
200716
3.55
0.41
1455
0.71
98.00
1.29


75110_01A07A
33.2
310941
200717
4.07
0.22
908
1.00
96.70
2.30


75110_01C18A
34.1
204727
200717
3.59
0.19
696
0.87
92.75
6.38


75110_01D24A
32.9
133815
200716
3.58
0.49
1759
1.78
96.86
1.36


75110_01E08A
36.5
112651
200716
3.66
0.24
883
2.96
95.00
2.05


75110_01G11A
39.0
164166
200716
3.48
0.22
779
1.70
96.04
2.26


75110_01H18A
48.8
100911
200716
3.95
0.34
1359
3.18
95.21
1.61


75110_01J09A
34.8
142980
200716
2.77
0.29
805
6.22
92.73
1.05


75110_01J17A
35.2
166740
200716
3.70
0.25
922
1.74
97.03
1.23


75110_01K10A
38.0
191431
200716
3.38
0.39
1299
1.43
97.01
1.56


75110_01L08A
35.3
208062
200716
3.91
0.27
1068
1.61
96.39
2.01


75110_01N04A
37.2
205484
200716
3.71
0.15
572
3.19
94.45
2.35


75110_02E08A
35.4
114945
200716
3.47
0.30
1026
7.05
92.76
0.19


75110_02E22A
32.8
268136
200717
2.36
0.14
337
1.74
94.75
3.51


75110_02I16A
36.1
144966
200716
3.16
0.45
1423
1.39
97.91
0.70


75110_02I18A
40.5
161770
200716
1.09
0.16
178
2.65
88.33
9.02


75110_02K11A
28.2
202868
200717
1.91
0.20
388
7.28
89.65
3.07


75110_02N15A
39.0
252617
200716
3.88
0.35
1367
1.35
97.57
1.08


75110_03B16A
34.2
90652
200716
2.18
0.19
417
3.37
85.18
11.45


75110_03C01A
36.1
169050
200716
2.93
0.18
522
4.92
90.63
4.45


75110_03D16A
35.6
206658
200717
3.57
0.40
1411
1.63
96.15
2.22


75110_03I08A
17.8
26145
200716
3.59
0.33
1166
1.45
97.05
1.50


75110_03I23A
26.2
67899
200717
1.15
0.15
168
1.33
95.59
3.08


75110_03L12A
36.8
162348
200716
4.01
0.41
1636
1.51
96.93
1.56


75110_04B08A
40.6
245613
200716
3.62
0.32
1139
0.98
97.50
1.52


75110_04D20A
33.2
241176
200717
2.83
0.37
1044
0.89
97.20
1.91


75110_04F22A
37.7
215983
200716
1.92
0.35
677
1.73
96.62
1.65


75110_04G02A
38.5
187393
200716
3.82
0.32
1236
3.61
94.30
2.10


75110_04G16A
36.3
240496
200716
3.59
0.24
864
1.46
92.63
5.91


75110_04H17A
28.8
151001
200717
4.06
0.37
1508
1.51
96.25
2.24


75110_04K10A
35.6
148953
200716
4.02
0.37
1493
2.28
97.02
0.70


75110_04P06A
36.9
240938
200716
3.96
0.19
736
1.83
95.73
2.44


75110_04P08A
36.4
127885
200721
2.93
0.44
1278
1.92
96.00
2.08


75110_05A11A
35.9
245571
200716
3.68
0.36
1320
0.06
99.09
0.85


75110_05B13A
55.8
135097
200716
3.01
0.51
1544
0.52
97.40
2.08


75110_05E05A
31.8
63987
200717
3.74
0.27
995
2.02
94.17
3.80


75110_05E13A
38.9
257219
200716
1.37
0.18
241
ND
86.35
13.65


75110_05F19A
37.1
155080
200716
2.15
0.19
399
1.08
96.26
2.66


75110_05G15A
31.6
325704
200717
3.25
0.29
931
1.54
94.27
4.20


75110_05K11A
38.1
111774
200716
1.99
0.31
620
3.40
92.79
3.82


75110_05L07A
37.9
156079
200716
3.80
0.43
1633
2.75
96.01
1.24


75110_06C16A
33.1
269944
200717
3.57
0.61
2194
1.33
96.94
1.72


75110_06D16A
39.2
253142
200721
1.66
0.10
161
0.82
95.63
3.55


75110_06E14A
31.7
224610
200717
3.85
0.31
1174
1.11
96.96
1.93


75110_06G04A
34.8
306560
200717
3.6
0.38
1368
0.66
99.34
ND


75110_06K03A
34.0
320202
200717
3.38
0.38
1279
10.02
88.03
1.94


75110_07B16A
37.3
189030
200716
1.12
0.19
214
2.77
95.19
2.04


75110_07E04A
36.1
141485
200716
1.30
0.30
386
2.62
93.97
3.41


75110_07H07A
37.1
204048
200716
3.77
0.32
1186
1.50
96.88
1.61


75110_07J02A
33.4
227689
200721
3.37
0.17
559
1.79
93.19
5.02


75110_07J24A
28.8
28372
200716
3.83
0.25
965
2.24
95.66
2.10


75110_07N04A
33.8
104160
200721
3.85
0.25
971
0.85
96.06
3.09


75110_08A13A
30.3
140031
200721
3.48
0.21
712
1.43
96.54
2.03


75110_08D24A
33.6
331704
200721
3.46
0.26
910
1.49
97.70
0.81


75110_08F20A
33.2
306832
200721
4.11
0.36
1462
3.26
95.34
1.40


75110_08G08A
32.2
324052
200721
3.61
0.40
1455
3.56
94.37
2.08


75110_08H06A
28.1
88823
200721
3.6
0.17
620
2.67
93.67
3.66


75110_08H11A
27.1
87025
200721
3.02
0.10
302
5.92
87.13
6.96


75110_08K12A
34.6
174702
200721
3.66
0.14
505
1.09
95.01
3.90


75110_08M20A
34.1
343164
200721
3.81
0.34
1285
2.13
96.06
1.81


75110_09G15A
37.3
236716
200716
3.96
0.36
1427
2.71
95.18
2.11


75110_09N20A
37.5
227238
200716
3.71
0.57
2123
1.47
97.12
1.41


75110_10K21A
29.0
118644
200721
4.06
0.32
1314
3.32
93.19
3.49


75110_10L22A
34.3
77406
200721
3.67
0.12
456
3.97
93.48
2.56


75110_10N21A
38.3
202650
200716
1.54
0.22
334
1.61
95.02
3.37


75110_10O16A
37.2
133087
200721
3.58
0.16
580
2.43
93.51
4.05


75110_11D03A
30.1
217408
200721
3.82
0.17
653
1.29
96.88
1.83


75110_12C19A
24.4
56480
200721
3.67
0.31
1128
2.10
95.09
2.80


75110_12H17A
37.3
196996
200716
3.78
0.33
1258
2.04
96.54
1.42


75110_12H19A
36.8
284458
200716
3.98
0.31
1237
2.78
95.83
1.38


75110_12K21A
37.2
146837
200716
3.34
0.45
1504
2.00
96.24
1.77


75110_13C07A
37.5
55986
200716
3.29
0.24
785
1.67
96.82
1.51


75110_13C13A
28.6
123167
200716
3.98
0.56
2241
2.82
95.99
1.19


75110_13P21A
27.2
31810
200721
3.51
0.21
745
3.37
93.04
3.59


75110_13P22A
37.5
184686
200717
3.88
0.28
1067
2.49
95.34
2.17


75110_14G10A
31.1
240647
200721
3.39
0.29
987
1.55
96.00
2.45


75110_14H13A
35.3
160296
200721
3.94
0.32
1260
0.61
96.84
2.56


75110_14I16A
33.2
297915
200721
4.02
0.20
787
0.69
97.20
2.10


75110_14N19A
32.5
264556
200721
3.81
0.12
450
2.62
93.98
3.40


75110_14P05A
28.6
93542
200721
1.47
0.23
337
2.24
94.64
3.12


75110_14P08A
28.3
58528
200721
3.18
0.38
1209
0.27
97.01
2.72









It will be appreciated by those skilled in the art that changes could be made to the embodiments described above without departing from the broad inventive concept thereof. It is understood, therefore, that this invention is not limited to the particular embodiments disclosed, but it is intended to cover modifications within the spirit and scope of the present invention as defined by the present description.

Claims
  • 1. An antibody that binds CD8 and/or CD4, wherein the antibody is: (A) an antibody that binds CD8, comprising: (1) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:31; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:32;(2) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:65; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:66;(3) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:99; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:100;(4) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:133; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:134;(5) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:167; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:168;(6) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:201; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:202;(7) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:235; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:236;(8) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:269; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:270;(9) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:303; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:304;(10) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:337; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:338;(11) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:371; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:372;(12) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:405; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:406;(13) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:439; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:440;(14) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:473; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:474;(15) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:507; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:508;(16) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:541; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:542;(17) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:575; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:576;(18) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:609; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:610;(19) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:643; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:644;(20) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:677; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:678;(21) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:711; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:712;(22) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:745; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:746;(23) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:779; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:780;(24) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:813; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:814;(25) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:847; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:848;(26) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:881; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:882;(27) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:915; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:916;(28) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:949; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:950;(29) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:983; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:984;(30) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1017; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1018;(31) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1051; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1052;(32) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1085; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1086;(33) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1119; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1120;(34) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1153; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1154;(35) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1187; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1188;(36) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1221; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1222;(37) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1255; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1256;(38) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1289; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1290;(39) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1323; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1324;(40) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1357; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1358;(41) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1391; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1392;(42) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1425; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1426;(43) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1459; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1460;(44) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1493; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1494;(45) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1527; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1528;(46) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1561; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1562;(47) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1595; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1596;(48) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1629; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1630;(49) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1663; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1664;(50) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1697; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1698;(51) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1731; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1732;(52) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1765; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1766;(53) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1799; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1800;(54) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1833; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1834;(55) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1867; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1868;(56) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1901; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1902;(57) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1935; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1936;(58) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1969; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1970;(59) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2003; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2004;(60) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2037; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2038;(61) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2071; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2072;(62) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2105; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2106;(63) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2139; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2140; or(64) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2173; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2174;(B) an antibody that binds CD4, comprising: (1) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2207; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2208;(2) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2241; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2242;(3) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2275; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2276;(4) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2309; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2310;(5) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2343; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2344;(6) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2377; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2378;(7) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2411; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2412;(8) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2445; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2446;(9) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2479; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2480;(10) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2513; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2514;(11) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2547; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2548;(12) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2581; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2582;(13) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2615; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2616;(14) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2649; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2650;(15) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2683; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2684;(16) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2717; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2718;(17) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2751; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2752;(18) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2785; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2786;(19) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2819; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2820;(20) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2853; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2854;(21) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2887; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2888;(22) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2921; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2922;(23) i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2955; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2956;(24) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2989; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2990;(25) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3023; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3024;(26) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3057; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3058;(27) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3091; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3092;(28) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3125; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3126;(29) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3159; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3160;(30) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3193; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3194;(31) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3227; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3228;(32) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3261; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3262;(33) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3295; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3296;(34) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3329; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3330;(35) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3363; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3364;(36) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3397; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3398;(37) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3431; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3432;(38) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3465; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3466;(39) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3499; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3500;(40) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3533; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3534;(41) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3567; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3568;(42) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3601; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3602;(43) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3635; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3636;(44) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3669; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3670;(45) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3703; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3704;(46) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3737; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3738;(47) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3771; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3772;(48) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3805; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3806;(49) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3839; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3840;(50) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3873; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3874;(51) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3907; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3908;(52) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3941; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3942;(53) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3975; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3976;(54) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4009; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4010;(55) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4043; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4044;(56) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4077; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4078; or(57) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4111; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4112;(58) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4145; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4146;(59) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4179; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4180;(60) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4213; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4214;(61) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4247; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4248;(62) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4281; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4282;(63) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4315; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4316;(64) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4349; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4350;(65) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4383; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4384;(66) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4417; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4418;(67) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4451; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4452;(68) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4485; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4486;(69) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4519; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4520;(70) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4553; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4554;(71) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4587; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4588;(72) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4621; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4622;(73) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4655; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4656;(74) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4689; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4690;(75) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4723; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4724;(76) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4757; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4758;(77) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4791; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4792;(78) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4825; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4826;(79) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4859; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4860;(80) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4893; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4894;(81) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4927; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4928; or(82) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4961; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4962; or(C) a multispecific antibody, wherein the multispecific antibody comprises: a first binding domain that binds to CD8 and a second binding domain that binds to CD4, wherein (a) the first binding domain that binds to CD8 comprises: (1) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:31; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:32;(2) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:65; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:66;(3) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:99; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:100;(4) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:133; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:134;(5) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:167; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:168;(6) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:201; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:202;(7) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:235; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:236;(8) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:269; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:270;(9) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:303; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:304;(10) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:337; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:338;(11) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:371; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:372;(12) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:405; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:406;(13) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:439; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:440;(14) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:473; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:474;(15) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:507; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:508;(16) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:541; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:542;(17) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:575; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:576;(18) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:609; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:610;(19) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:643; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:644;(20) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:677; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:678;(21) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:711; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:712;(22) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:745; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:746;(23) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:779; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:780;(24) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:813; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:814;(25) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:847; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:848;(26) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:881; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:882;(27) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:915; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:916;(28) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:949; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:950;(29) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:983; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:984;(30) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1017; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1018;(31) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1051; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1052;(32) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1085; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1086;(33) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1119; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1120;(34) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1153; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1154;(35) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1187; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1188;(36) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1221; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1222;(37) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1255; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1256;(38) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1289; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1290;(39) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1323; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1324;(40) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1357; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1358;(41) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1391; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1392;(42) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1425; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1426;(43) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1459; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1460;(44) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1493; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1494;(45) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1527; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1528;(46) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1561; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1562;(47) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1595; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1596;(48) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1629; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1630;(49) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1663; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1664;(50) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1697; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1698;(51) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1731; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1732;(52) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1765; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1766;(53) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1799; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1800;(54) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1833; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1834;(55) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1867; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1868;(56) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1901; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1902;(57) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1935; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1936;(58) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:1969; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:1970;(59) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2003; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2004;(60) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2037; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2038;(61) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2071; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2072;(62) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2105; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2106;(63) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2139; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2140; or(64) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2173; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2174; and(b) the second binding domain that binds to CD4 comprises: (1) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2207; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2208;(2) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2241; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2242;(3) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2275; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2276;(4) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2309; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2310;(5) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2343; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2344;(6) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2377; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2378;(7) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2411; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2412;(8) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2445; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2446;(9) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2479; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2480;(10) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2513; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2514;(11) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2547; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2548;(12) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2581; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2582;(13) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2615; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2616;(14) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2649; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2650;(15) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2683; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2684;(16) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2717; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2718;(17) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2751; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2752;(18) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2785; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2786;(19) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2819; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2820;(20) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2853; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2854;(21) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2887; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2888;(22) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2921; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2922;(23) i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2955; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2956;(24) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:2989; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:2990;(25) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3023; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3024;(26) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3057; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3058;(27) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3091; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3092;(28) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3125; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3126;(29) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3159; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3160;(30) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3193; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3194;(31) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3227; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3228;(32) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3261; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3262;(33) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3295; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3296;(34) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3329; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3330;(35) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3363; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3364;(36) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3397; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3398;(37) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3431; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3432;(38) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3465; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3466;(39) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3499; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3500;(40) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3533; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3534;(41) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3567; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3568;(42) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3601; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3602;(43) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3635; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3636;(44) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3669; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3670;(45) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3703; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3704;(46) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3737; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3738;(47) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3771; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3772;(48) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3805; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3806;(49) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3839; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3840;(50) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3873; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3874;(51) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3907; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3908;(52) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3941; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3942;(53) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:3975; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:3976;(54) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4009; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4010;(55) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4043; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4044;(56) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4077; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4078; or(57) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4111; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4112;(58) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4145; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4146;(59) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4179; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4180;(60) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4213; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4214;(61) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4247; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4248;(62) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4281; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4282;(63) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4315; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4316;(64) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4349; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4350;(65) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4383; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4384;(66) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4417; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4418;(67) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4451; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4452;(68) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4485; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4486;(69) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4519; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4520;(70) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4553; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4554;(71) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4587; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4588;(72) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4621; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4622;(73) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:4655; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:4656;(74) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4689; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4690;(75) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4723; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4724;(76) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4757; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4758;(77) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4791; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4792;(78) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4825; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4826;(79) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4859; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4860;(80) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4893; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4894;(81) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4927; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4928; or(82) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of SEQ ID NO:4961; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of SEQ ID NO:4962.
  • 2. The antibody of claim 1, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to (i) the Kabat numbering system;(ii) the Chothia numbering system;(iii) the AbM numbering system;(iv) the Contact numbering system; or(v) the IMGT numbering system.
  • 3. The antibody of claim 1, wherein the antibody is a humanized antibody.
  • 4. The antibody of claim 1, wherein the antibody is an IgG antibody, and wherein optionally the IgG antibody is an IgG1, IgG2, IgG3 or IgG4 antibody.
  • 5. The antibody of claim 1, wherein the antibody comprises (i) a kappa light chain or (ii) a lambda light chain.
  • 6. The antibody of claim 1, wherein the antibody is a monoclonal antibody.
  • 7. The antibody of claim 1, wherein: (A) (i) the antibody that binds to CD8 binds a CD8 antigen or a CD8 epitope, wherein optionally the antibody specifically binds the CD8 antigen or CD8 epitope; (ii) the antibody that binds to CD4 binds a CD4 antigen or a CD4 epitope, wherein optionally the antibody specifically binds the CD4 antigen or CD4 epitope; or(iii) the multispecific antibody that binds to CD8 and CD4 comprises a first binding domain that binds to a CD8 antigen or a CD8 epitope, and a second binding domain that binds to a CD4 antigen or a CD4 epitope;wherein optionally (a) the first binding domain specifically binds the CD8 antigen or CD8 epitope,(b) the second binding domain specifically binds the CD4 antigen or CD4 epitope, or(c) the first binding domain specifically binds the CD8 antigen or CD8 epitope, and the second binding domain specifically binds the CD4 antigen or CD4 epitope; or(B) (i) the CD8 is present on the surface of a T cell; (ii) the CD4 is present on the surface of a T cell; or(iii) both the CD8 and CD4 are present on the surface of a T cell.
  • 8. The antibody of claim 1, wherein (i) the antibody that binds to CD8(a) binds to CD8α,wherein optionally the antibody binds a CD8α antigen or a CD8α epitope,wherein optionally the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 form a binding site for an antigen of the CD8α or an epitope of the CD8a;(b) binds to CD8β,wherein optionally the antibody binds a CD8β antigen or a CD8β epitope,wherein optionally the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 form a binding site for an antigen of the CD8β or an epitope of the CD8β; or(c) binds at the interface of CD8α and CD8β,wherein optionally the antibody binds an antigen or an epitope at the interface of the CD8α and CD8β,wherein optionally the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 form a binding site for an antigen at the interface of the CD8α and CD8β or form a binding site for an epitope at the interface of the CD8α and CD8β;(ii) the first binding domain of the multispecific antibody(a) binds to CD8α,wherein optionally the first binding domain binds a CD8α antigen or a CD8α epitope,wherein optionally the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the first binding domain form a binding site for an antigen of the CD8α or an epitope of the CD8α;(b) binds to CD8β,wherein optionally the first binding domain binds a CD8β antigen or a CD8β epitope,wherein optionally the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the first binding domain form a binding site for an antigen of the CD8β or an epitope of the CD8β; or(c) binds at the interface of CD8α and CD8β,wherein optionally the first binding domain binds an antigen or an epitope at the interface of the CD8α and CD8β,wherein optionally the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 form a binding site for an antigen at the interface of the CD8α and CD8β or form a binding site for an epitope at the interface of the CD8α and CD8β.
  • 9. The antibody of claim 1, wherein (i) the antibody is multivalent,wherein optionally the antibody binds to at least three antigens, at least four antigens, or at least five antigens; or(ii) the antibody is a multispecific antibody,wherein optionally the multispecific antibody is a bispecific antibody, a trispecific antibody, or a quadraspecific antibody.
  • 10. The antibody of claim 1, wherein (A) the antibody that binds to CD8 is a multispecific CD8 antibody, wherein the multispecific CD8 antibody comprises: (a) a first binding domain that binds CD8, and a second binding domain that binds to a second target, wherein optionally(i) the second target is CD4,(ii) the second target is a T cell receptor (TCR) complex or(iii) the second target is a T cell costimulatory molecule(b) a first binding domain that binds CD8, a second binding domain that binds to a second target, and a third binding domain that binds to a third target, wherein optionally(i) the second target is CD4,(ii) the second target is a TCR complex(iii) the second target is a T cell costimulatory molecule(iv) the second target is CD4, and the third target is a TCR complex,(v) the second target is CD4, and the third target is a T cell costimulatory molecule or(vi) the second target is a TCR complex and the third target is a T cell costimulatory molecule or(c) a first binding domain that binds CD8, and a second binding domain that binds to a second target, a third binding domain that binds to a third target, and a fourth binding domain that binds to a fourth target, wherein optionally(i) the second target is CD4,(ii) the second target is a TCR complex or(iii) the second target is a T cell costimulatory molecule(iv) the second target is CD4, and the third target is a TCR complex(v) the second target is CD4, and the third target is a T cell costimulatory molecule(vi) the second target is a TCR complex and the third target is a T cell costimulatory molecule or(vii) the second target is CD4, the third target is a TCR complex andthe fourth target is a T cell costimulatory molecule(B) the antibody that binds to CD4 is a multispecific CD4 antibody, wherein the multispecific CD4 antibody comprises: (a) a first binding domain that binds CD4, and a second binding domain that binds to a second target, wherein optionally(i) the second target is CD8,(ii) the second target is a T cell receptor (TCR) complex or(iii) the second target is a T cell costimulatory molecule(b) a first binding domain that binds CD4, a second binding domain that binds to a second target, and a third binding domain that binds to a third target, wherein optionally(i) the second target is CD8,(ii) the second target is a TCR complex(iii) the second target is a T cell costimulatory molecule(iv) the second target is CD8, and the third target is a TCR complex(v) the second target is CD8, and the third target is a T cell costimulatory molecule(vi) the second target is a TCR complex and the third target is a T cell costimulatory molecule or(c) a first binding domain that binds CD4, and a second binding domain that binds to a second target, a third binding domain that binds to a third target, and a fourth binding domain that binds to a fourth target, wherein optionally(i) the second target is CD8,(ii) the second target is a TCR complex or(iii) the second target is a T cell costimulatory molecule(iv) the second target is CD8, and the third target is a TCR complex(v) the second target is CD8, and the third target is a T cell costimulatory molecule(vi) the second target is a TCR complex and the third target is a T cell costimulatory molecule or(vii) the second target is CD8, the third target is a TCR complex-andthe fourth target is a T cell costimulatory molecule-or(C) the multispecific antibody that binds to CD8 and CD4, comprises: (a) a first binding domain that binds CD8, and a second binding domain that binds to CD4, and a third binding domain that binds to a third target; wherein optionally(i) the third target is a TCR complex or(ii) the third target is a T cell costimulatory molecule or(b) a first binding domain that binds CD8, and a second binding domain that binds to CD4, a third binding domain that binds to a third target, and a fourth binding domain that binds to a fourth target, wherein optionallythe third target is a TCR complex andthe fourth target is a T cell costimulatory molecule.
  • 11. The antibody of claim 10, wherein (i) the TCR complex comprises CD3, CD3ε, CD3γ, CD3δ, CD3ζ, a TCRα chain, a TCRβ chain, a TCRγ chain, or a TCRδ chain, or(ii) the T cell costimulatory molecule comprises CD28, CTLA4, ICOS, 4-1BB, GITR, CD27, OX40, CD40L, HVEM, Galectin-9, TIM-1, LFA1, CD2, or PD1.
  • 12. A nucleic acid sequence encoding one or more VH or VL of the antibody of claim 1.
  • 13. A vector comprising the nucleic acid of claim 12.
  • 14. A host cell comprising the vector of claim 13.
  • 15. A kit comprising the vector of claim 13 and packaging for the same.
  • 16. A kit comprising the antibody of claim 1 and packaging for the same.
  • 17. A pharmaceutical composition comprising the antibody of claim 1, and a pharmaceutically acceptable carrier.
  • 18. A method of producing the pharmaceutical composition of claim 17, comprising combining the antibody with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition.
  • 19. A method of activating a T cell, comprising contacting the T cell with the antibody of claim 1.
  • 20. A method of enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting a cell, wherein (A) the cell is a CD8-expressing cell, wherein the method comprises: (i) providing a sample comprising the CD8-expressing cell; contacting the sample with the CD8 antibody of claim 1; and enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD8-expressing cell bound to the CD8 antibody,(ii) contacting a CD8-expressing cell with the CD8 antibody of claim 1; and enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD8-expressing cell bound to the CD8 antibody, or(iii) contacting a CD8-expressing cell with the CD8 antibody of claim 1; and enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD8-expressing cell based on binding of the CD8-expressing cell to the CD8 antibody,wherein optionally the CD8-expressing cell is a T cell,wherein optionally the T cell is CD8+ cytotoxic T lymphocyte (CTL);(B) the cell is a CD4-expressing cell, wherein the method comprises: (i) providing a sample comprising the CD4-expressing cell; contacting the sample with the CD4 antibody of claim 1; and enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD4-expressing cell bound to the CD4 antibody,(ii) contacting a CD4-expressing cell with the CD4 antibody of claim 1; and enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD4-expressing cell bound to the CD4 antibody, or(iii) contacting a CD4-expressing cell with the CD4 antibody of claim 1; and enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD4-expressing cell based on binding of the CD4-expressing cell to the CD4 antibody,wherein optionally the CD4-expressing cell is a T cell,wherein optionally, the T cell is a CD4+T helper cell; or(C) the cell is a CD4-expressing cell and/or a CD8-expressing cell, wherein the method comprises: (i) providing a sample comprising the CD4-expressing cells and/or CD8-expressing cells; contacting the sample with the multispecific antibody that binds to CD8 and CD4 of claim 1; and enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD4-expressing cells and/or CD8-expressing cells bound to the multispecific antibody,(ii) contacting CD4-expressing cells and/or CD8-expressing cells with the multispecific antibody that binds to CD8 and CD4 of claim 1; and enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD4-expressing cells and/or CD8-expressing cells bound to the multispecific antibody, or(iii) contacting CD4-expressing cells and/or CD8-expressing cells with the multispecific antibody that binds to CD8 and CD4 of claim 1; andenriching, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD4-expressing cells and/or CD8-expressing cells based on binding of the CD4-expressing cells and/or CD8-expressing cells to the multispecific antibody,wherein optionally the CD4-expressing cells and/or CD8-expressing cells are T cells,wherein optionally the CD4-expressing cells are CD4+T helper cells,wherein optionally the CD8-expressing cells are CD8+ CTL.
  • 21. The method of claim 20, wherein the cell is provided as a sample comprising a population of cells, wherein optionally the cells are lymphocytes,wherein optionally the lymphocytes are T cells; orwherein optionally the sample is a blood sample or a tissue sample.
CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Ser. No. 63/091,078 filed Oct. 13, 2020, the disclosure of which is incorporated by reference herein in its entirety.

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Related Publications (1)
Number Date Country
20220112288 A1 Apr 2022 US
Provisional Applications (1)
Number Date Country
63091078 Oct 2020 US