Claims
- 1. An isolated nucleic acid encoding a protein which binds CD28 or CTLA4 comprising a contiguous nucleotide sequence derived from at least one T cell costimulatory molecule gene, the nucleotide sequence represented by a formula A-B-C-D-E, wherein
A comprises a nucleotide sequence of at least one first exon of a T cell costimulatory molecule gene, wherein the at least one first exon encodes a signal peptide domain, B comprises a nucleotide sequence of at least one second exon of a T cell costimulatory molecule gene, wherein the at least one second exon encodes an immunoglobulin variable region-like domain, C comprises a nucleotide sequence of at least one third exon of a T cell costimulatory molecule gene, wherein the at least one third exon encodes an immunoglobulin constant region-like domain, D comprises a nucleotide sequence of at least one fourth exon of a T cell costimulatory molecule gene, wherein the at least one fourth exon encodes a transmembrane domain, and E comprises a nucleotide sequence of at least one fifth exon of a T cell costimulatory molecule gene, wherein the at least one fifth exon encodes a cytoplasmic domain, with the proviso that E does not comprise a nucleotide sequence selected from a group consisting of SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29 and SEQ ID NO:31.
- 2. The isolated nucleic acid of claim 1 which is a cDNA.
- 3. The isolated nucleic acid of claim 2 which comprises a coding region of the cDNA.
- 4. The isolated nucleic acid of claim 1, wherein the nucleotide sequence is derived from a T cell costimulatory molecule gene encoding B7-1.
- 5. The isolated nucleic acid of claim 4, wherein B7-1 is murine.
- 6. The isolated nucleic acid of claim 4, wherein B7-1 is human.
- 7. The isolated nucleic acid of claim 5, wherein E comprises a nucleotide sequence shown in SEQ ID NO:4.
- 8. The isolated nucleic acid of claim 5, wherein E comprises a nucleotide sequence encoding an amino acid sequence shown in SEQ ID NO:5.
- 9. An isolated nucleic acid encoding a protein which binds CD28 or CTLA4 and is encoded by a T cell costimulatory molecule gene having
at least one first exon encoding a first cytoplasmic domain comprising a nucleotide sequence selected from the group consisting of a nucleotide sequence of SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29 and SEQ ID NO:31, and at least one second exon encoding a second cytoplasmic domain, wherein the isolated nucleic acid comprises a nucleotide sequence encoding the second cytoplasmic domain.
- 10. The isolated nucleic acid of claim 9 which comprises a coding region of a cDNA.
- 11. The isolated nucleic acid of claim 9 which does not comprise a nucleotide sequence encoding the first cytoplasmic domain.
- 12. The isolated nucleic acid of claim 9 wherein the T cell costimulatory molecule gene is B7-1.
- 13. The isolated nucleic acid of claim 12 wherein B7-1 is murine.
- 14. The isolated nucleic acid of claim 12 wherein B7-1 is human.
- 15. An isolated nucleic acid encoding a protein which binds CD28 or CTLA4 comprising a nucleotide sequence shown in SEQ ID NO: 1.
- 16. An isolated nucleic acid encoding a protein which binds CD28 or CTLA4 comprising a nucleotide sequence shown in SEQ ID NO:3.
- 17. An isolated nucleic acid encoding a cytoplasmic domain derived from a protein which binds CD28 or CTLA4, the nucleic acid comprising a nucleotide sequence shown in SEQ ID NO:4.
- 18. An isolated protein which binds to CD28 or CTLA4 having an amino acid sequence derived from amino acid sequences encoded by at least one T cell costimulatory molecule gene, the protein comprising a contiguous amino acid sequence represented by a formula A-B-C-D-E, wherein
A, which may or may not be present, comprises an amino acid sequence of a signal peptide domain encoded by at least one exon of a T cell costimulatory molecule gene, B comprises an amino acid sequence of an immunoglobulin variable region-like domain encoded by at least one exon of a T cell costimulatory molecule gene, C comprises an amino acid sequence of an immunoglobulin constant region-like domain encoded by at least one exon of aT cell costimulatory molecule gene, D comprises an amino acid sequence of a transmembrane domain encoded by at least one exon of a T cell costimulatory molecule gene, and E comprises an amino acid sequence of a cytoplasmic domain encoded by at least one exon of a T cell costimulatory molecule gene, with the proviso that E not comprise an amino acid sequence selected from the group consisting of SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30 and SEQ ID NO:32.
- 19. The isolated protein of claim 18 which is B7-1.
- 20. The isolated protein of claim 19 which is murine.
- 21. The isolated protein of claim 19 which is human.
- 22. The isolated protein of claim 20, wherein E comprises an amino acid sequence shown in SEQ ID NO:5.
- 23. An isolated protein which binds CD28 or CTLA4 and is encoded by a T cell costimulatory molecule gene having
at least one first exon encoding a first cytoplasmic domain comprising an amino acid sequence selected from the group consisting of an amino acid sequence of SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, and SEQ ID NO:32, and at least one second exon encoding a second cytoplasmic domain, wherein the T cell costimulatory molecule comprises the second cytoplasmic domain.
- 24. The isolated protein of claim 23 which does not comprise the first cytoplasmic domain.
- 25. The isolated protein of claim 23 which is B7-1.
- 26. The isolated protein of claim 25 which is murine.
- 27. The isolated protein of claim 25 which is human.
- 28. An isolated protein which binds CD28 or CTLA4 comprising an amino acid sequence shown in SEQ ID NO:2.
- 29. An isolated cytoplasmic domain polypeptide derived from a protein which binds CD28 or CTLA4, the polypeptide comprising an amino acid sequence shown in SEQ ID NO:5.
- 30. A recombinant expression vector comprising the nucleic acid molecule of claim 15.
- 31. A host cell which contains the recombinant expression vector of claim 30.
- 32. An antibody which binds to the murine B7-1 cytoplasmic domain polypeptide of claim 29.
- 33. An isolated nucleic acid encoding a protein which binds CD28 or CTLA4 comprising a contiguous nucleotide sequence derived from at least one T cell costimulatory molecule gene, the nucleotide sequence represented by a formula A-B-C-D-E, wherein
A comprises a nucleotide sequence of at least one first exon of a T cell costimulatory molecule gene, wherein the at least one first exon encodes a signal peptide domain, B comprises a nucleotide sequence of at least one second exon of a T cell costimulatory molecule gene, wherein the at least one second exon encodes an immunoglobulin variable region-like domain, C comprises a nucleotide sequence of at least one third exon of a T cell costimulatory molecule gene, wherein the at least one third exon encodes an immunoglobulin constant region-like domain, D, which may or may not be present, comprises a nucleotide sequence of at least one fourth exon of a T cell costimulatory molecule gene, wherein the at least one fourth exon encodes a transmembrane domain, and E, which may or may not be present, comprises a nucleotide sequence of at least one fifth exon of a T cell costimulatory molecule gene, wherein the at least one fifth exon encodes a cytoplasmic domain, with the proviso that A does not comprise a nucleotide sequence selected from a group consisting of SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39 and SEQ ID NO:41.
- 34. The isolated nucleic acid of claim 33 which is a cDNA.
- 35. The isolated nucleic acid of claim 34 which comprises a coding region of the cDNA.
- 36. The isolated nucleic acid of claim 33, wherein the nucleotide sequence is derived from a T cell costimulatory molecule gene encoding B7-2.
- 37. The isolated nucleic acid of claim 36, wherein B7-2 is murine.
- 38. The isolated nucleic acid of claim 36, wherein B7-2 is human.
- 39. The isolated nucleic acid of claim 37, wherein A comprises a nucleotide sequence selected from the group consisting of SEQ ID NO:14.
- 40. An isolated nucleic acid encoding a protein which binds CD28 or CTLA4 and is encoded by a T cell costimulatory molecule gene having
at least one first exon encoding a first signal peptide domain comprising a nucleotide sequence selected from the group consisting of a nucleotide sequence of SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37 SEQ ID NO:39 and SEQ ID NO:41, and at least one second exon encoding a second signal peptide domain, wherein the isolated nucleic acid comprises a nucieotide sequence encoding the second signal peptide domain.
- 41. The isolated nucleic acid of claim 40 which comprises a coding region of a cDNA.
- 42. The isolated nucleic acid of claim 40 which does not comprise a nucleotide sequence encoding the first signal peptide domain.
- 43. The isolated nucleic acid of claim 40 wherein the T cell costimulatory molecule gene is B7-2.
- 44. The isolated nucleic acid of claim 43 wherein B7-2 is murine.
- 45. The isolated nucleic acid of claim 43 wherein B7-2 is human.
- 46. An isolated nucleic acid encoding a protein which binds CD28 or CTLA4 comprising a nucleotide sequence shown in SEQ ID NO:12.
- 47. An isolated nucleic acid encoding a signal peptide domain derived from a protein which binds CD28 or CTLA4, the nucleic acid comprising a nucleotide sequence shown in SEQ ID NO:14.
- 48. An isolated protein which binds CD28 or CTLA4 having an amino acid sequence derived from amino acid sequences encoded by at least one T cell costimulatory molecule gene, the protein comprising a contiguous amino acid sequence represented by a formula A-B-C-D-E, wherein
A comprises an amino acid sequence of a signal peptide domain encoded by at least one exon of a T cell costimulatory molecule gene, B comprises an amino acid sequence of an immunoglobulin variable region-like domain encoded by at least one exon of a T cell costimulatory molecule gene, C comprises an amino acid sequence of an immunoglobulin constant region-like domain encoded by at least one exon of aT cell costimulatory molecule gene, D, which may or may not be present, comprises an amino acid sequence of a transmembrane domain encoded by at least one exon of a T cell costimulatory molecule gene, and E, which may or may not be present, comprises an amino acid sequence of a cytoplasmic domain encoded by at least one exon of a T cell costimulatory molecule gene, with the proviso that A not comprise an amino acid sequence selected from the group consisting of SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38 and SEQ ID NO:40.
- 49. The isolated protein of claim 48 which is B7-2.
- 50. The isolated protein of claim 49 which is murine.
- 51. The isolated protein of claim 49 which is human.
- 52. The isolated protein of claim 50, wherein A comprises an amino acid sequence shown in SEQ ID NO: 15.
- 53. An isolated protein which binds CD28 or CTLA4 and is encoded by a T cell costimulatory molecule gene having
at least one first exon encoding a first signal peptide domain comprising an amino acid sequence selected from the group consisting of an amino acid sequence of SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40 and SEQ ID NO:42, and at least one second exon encoding a second signal peptide domain, wherein the T cell costimulatory molecule comprises the second signal peptide domain.
- 54. The isolated protein of claim 53 which does not comprise the first signal peptide domain.
- 55. The isolated protein of claim 53 which is B7-2.
- 56. The isolated protein of claim 55 which is murine.
- 57. The isolated protein of claim 55 which is human.
- 58. An isolated protein wnich binds CD28 or CTLA4 comprising an amino acid sequence shown in SEQ ID NO:13.
- 59. An isolated signal peptide domain polypeptide derived from a protein which binds CD28 or CTLA4, the polypeptide comprising an amino acid sequence shown in SEQ ID NO:15.
- 60. A recombinant expression vector comprising the nucleic acid molecule of claim 46.
- 61. A host cell which contains the recombinant expression vector of claim 60.
- 62. An antibody which binds to the polypeptide of claim 59.
- 63. An isolated nucleic acid encoding a protein comprising a contiguous nucleotide sequence derived from at least one T cell costimulatory molecule gene, the nucleotide sequence represented by a formula A-B-C-D, wherein
A comprises a nucleotide sequence of at least one first exon of a T cell costimulatory molecule gene, wherein the at least one first exon encodes a signal peptide domain, B comprises a nucleotide sequence of at least one second exon of a T cell costimulatory molecule gene, wherein the at least one second exon encodes an immunoglobulin constant region-like domain, C comprises a nucleotide sequence of at least one third exon of a T cell costimulatory molecule gene, wherein the at least one third exon encodes a transmembrane domain, and D comprises a nucleotide sequence of at least one fourth exon of a T cell costimulatory molecule gene, wherein the at least one fourth exon encodes a cytoplasmic domain.
- 64. The isolated nucleic acid of claim 63 comprising a nucleotide sequence shown in SEQ ID NO:8.
- 65. The isolated nucleic acid of claim 63 comprising a nucleotide sequence shown in SEQ ID NO:10.
- 66. An isolated protein having an amino acid sequence derived from amino acid sequences encoded by at least one T cell costimulatory molecule gene, the protein comprising a contiguous amino acid sequence represented by a formula A-B-C-D, wherein
A, which may or may not be present, comprises an amino acid sequence of a signal peptide domain encoded by at least one exon of a T cell costimulatory molecule gene, B comprises an amino acid sequence of an immunoglobulin constant region-like domain encoded by at least one exon of a T cell costimulatory molecule gene, and C comprises an amino acid sequence of a transmembrane domain encoded by at least one exon of a T cell costimulatory molecule gene, and D comprises an amino acid sequence of a cytoplasmic domain encoded by at least one exon of a T cell costimulatory molecule gene.
- 67. The isolated protein of claim 66 comprising an amino acid sequence shown in SEQ ID NO:9.
- 68. The isolated protein of claim 66 comprising an amino acid sequence shown in SEQ ID NO:11.
GOVERNMENT FUNDING
[0001] Work described herein was supported under CA-40216 and GM46883 awarded by the National Instiutes of Health. The U.S. government therefore may have certain rights in this invention.
Divisions (1)
|
Number |
Date |
Country |
Parent |
08205697 |
Mar 1994 |
US |
Child |
09837867 |
Apr 2001 |
US |