Claims
- 1. An isolated nucleic acid molecule comprising a nucleotide sequence encoding a CD100 antigen.
- 2. The isolated nucleic acid molecule of claim 1, which is a cDNA.
- 3. The isolated nucleic acid molecule of claim 2, wherein the CD100 antigen is human.
- 4. The nucleic acid of claim 3 comprising a nucleotide sequence shown in FIG. 1, SEQ ID NO: 1.
- 5. The isolated nucleic acid of claim 4 comprising the coding region.
- 6. The isolated nucleic acid of claim 3 derived from a hematopoietic cell which hybridizes under high stringency conditions to a nucleic acid molecule comprising a nucleotide sequence shown in FIG. 1, SEQ ID NO: 1.
- 7. An isolated nucleic molecule comprising a nucleotide sequence encoding a protein wherein the protein comprises an amino acid sequence having at least about 80% overall amino acid sequence identity with an amino acid sequence shown in FIG. 2, SEQ ID NO: 2.
- 8. The isolated nucleic acid molecule of claim 7, wherein the protein has a CD100 activity.
- 9. An isolated nucleic acid molecule encoding an amino acid sequence shown in FIG. 2, SEQ ID NO: 2.
- 10. An isolated nucleic acid molecule comprising a nucleotide sequence encoding a protein, wherein the protein comprises a semaphorin domain having an amino acid sequence at least 80% identical to an amino acid sequence in FIG. 2, SEQ ID NO: 2.
- 11. An isolated nucleic acid molecule comprising a nucleotide sequence encoding a protein, wherein the protein comprises
a) a semaphorin domain having an amino acid sequence at least 60% identical to an amino acid sequence shown in FIG. 2, SEQ ID NO: 2; and b) an immunoglobulin-like domain having an amino acid sequence at least 50% identical to an amino acid sequence shown in FIG. 2, SEQ ID NO: 2.
- 12. The isolated nucleic acid molecule of claim 11, further comprising
c) a cytoplasmic domain having an amino acid sequence at least 50% identical to an amino acid sequence shown in FIG. 2, SEQ ID NO: 2.
- 13. An isolated nucleic acid molecule comprising a nucleotide sequence encoding a protein, wherein the protein comprises an extracellular domain having an amino acid sequence at least 80% identical to a amino acid sequence shown in FIG. 2, SEQ ID NO: 2.
- 14. An isolated nucleic acid molecule encoding a CD100 fusion protein comprising a nucleotide sequence encoding a first peptide having an amino acid sequence at least 80% identical to an amino acid sequence shown in FIG. 2, SEQ ID NO: 2 and a nucleic sequence encoding a second peptide corresponding to a moiety that alters the solubility, binding affinity or valency of the first peptide.
- 15. The isolated nucleic acid molecule of claim 14, wherein the first peptide comprises an extracellular domain of a human CD100 antigen.
- 16. The isolated nucleic acid molecule of claim 14, wherein the first peptide comprises a semaphorin domain of human CD100 antigen.
- 17. The isolated nucleic acid molecule of claim 14, wherein the second peptide comprises an immunoglobulin constant region.
- 18. An isolated nucleic acid molecule comprising a nucleotide sequence encoding a peptide comprising a fragment of at least about 30 amino acids of the sequence shown in FIG. 2, SEQ ID NO: 2.
- 19. The isolated nucleic acid molecule of claim 18, wherein the peptide has a CD100 activity.
- 20. An isolated nucleic acid molecule of claim 1, which is antisense to the nucleic acid molecule of claim 1.
- 21. An isolated nucleic acid molecule of claim 1, which is antisense to the nucleic acid molecule of claim 4.
- 31. An isolated nucleic acid molecule of claim 1, which is antisense to the nucleic acid molecule of claim 5.
- 32. A vector comprising a nucleotide sequence encoding a CD100 antigen.
- 33. A vector comprising a nucleotide sequence encoding a protein comprising an amino acid sequence shown in FIG. 2, SEQ ID NO: 2.
- 34. A host cell comprising the vector of claim 32.
- 35. A host cell comprising the vector of claim 33.
- 36. A method for producing a CD100 antigen comprising culturing a host cell of claim 34 in a suitable medium such that the CD100 antigen is produced.
- 37. A method for producing a CD100 antigen comprising culturing a host cell of claim 35 in a suitable medium such that the CD100 antigen is produced.
- 38. An isolated protein having a CD100 activity.
- 39. The isolated protein of claim 38, which is human.
- 40. The isolated protein of claim 39, wherein the protein comprises an amino acid sequence having at least about 80% overall amino acid sequence identity with an amino acid sequence shown in FIG. 2 (SEQ ID NO: 2).
- 41. The isolated protein of claim 40, wherein the protein comprises an amino acid sequence having at least about 90% overall amino acid sequence identity with an amino acid sequence shown in FIG. 2 (SEQ ID NO: 2).
- 42. The isolated protein of claim 40, wherein the protein comprises an amino acid sequence having at least about 95% overall amino acid sequence identity with an amino acid sequence shown in FIG. 2 (SEQ ID NO: 2).
- 43. The isolated protein of claim 39, wherein the protein CD100 activity.
- 44. The isolated protein of claim 43, which comprises an amino acid sequence shown in FIG. 2 (SEQ ID NO: 2).
- 45. An isolated protein comprising a semaphorin domain having an amino acid sequence at least 80% identical to an amino acid sequence shown in FIG. 2 (SEQ ID NO: 2).
- 46. The isolated protein of claim 45 having an amino acid sequence at least 90% identical to an amino acid sequence shown in FIG. 2 (SEQ ID NO: 2).
- 47. An isolated protein comprising
a) a semaphorin domain having an amino acid sequence at least 60% identical to an amino acid sequence shown in FIG. 2 SEQ ID NO: 2); and b) an immunoglobulin-like domain having an amino acid sequence that is at least 50% identical to an amino acid sequence shown in FIG. 2 (SEQ ID NO: 2).
- 48. The isolated protein of claim 47, further comprising
c) a cytoplasmic domain having an amino acid sequence at least 50% identical to amino acid sequence shown in FIG. 2 (SEQ ID NO: 2).
- 49. An isolated protein comprising an extracellular domain having an amino acid sequence at least 80% identical to an amino acid sequence shown in FIG. 2, SEQ ID NO: 2.
- 50. An CD100 fusion protein comprising a first peptide having an amino acid sequence at least 80% identical to an amino acid sequence shown in FIG. 2, SEQ ID NO: 2 and a second peptide corresponding to a moiety that alters the solubility, binding affinity or valency of the first peptide.
- 51. The fusion protein of claim 50, wherein the first peptide comprises an extracellular domain of a human CD100 antigen.
- 52. The fusion protein of claim 50, wherein the first peptide comprises a semaphorin domain of a human CD100 antigen.
- 53. The fusion protein of claim 50, wherein the second peptide comprises an immunoglobulin constant region.
- 54. A peptide comprising a fragment of at least about 30 amino acids of the sequence shown in FIG. 2, SEQ ID NO: 2.
- 55. The peptide of claim 54, which has a CD100 activity.
- 56. The peptide of claim 54, wherein the fragment is at least about 40 amino acids in length.
- 57. The peptide of claim 56 which has a CD100 activity.
- 58. The peptide of claim 56, wherein the fragment is at least about 50 amino acid in length.
- 59. The peptide of claim 58, which has a CD100 activity.
- 60. A pharmaceutical composition comprising the protein of claim 44 and a pharmaceutically acceptable carrier.
- 61. A pharmaceutical composition comprising the protein of claim 50 and a pharmaceutically acceptable carrier.
- 62. A pharmaceutical composition comprising the protein of claim 55 and a pharmaceutically acceptable carrier.
- 63. A vaccine composition comprising at least one antigen and a first agent which stimulates a CD100 ligand-associated signal.
- 64. The composition of claim 63, further comprising a second agent which stimulates a CD40-associated signal.
- 65. A method for modulating a B cell response comprising contacting the B cell with an agent which modulates a CD100 ligand-associated signal in the B cell, such that a response by the B cell is modulated.
- 66. The method of claim 65, wherein the agent stimulates a CD100 ligand associated signal, such that a response by the B cell is stimulated.
- 67. The method of claim 66, wherein the agent is a stimulatory form of a CD100 antigen.
- 68. The method of claim 67, wherein the stimulatory form of a CD100 antigen is a soluble form of a CD100 antigen.
- 69. The method of claim 68, wherein the soluble form of a CD100 antigen is an immunoglobulin fusion protein.
- 70. The method of claim 67, wherein the stimulatory form of a CD100 antigen is attached to a solid phase support.
- 71. The method of claim 68, wherein the solid phase support is a cell membrane.
- 72. The method of claim 66, further comprising contacting the B cell with a second agent which provides a stimulatory signal to the B cell.
- 73. The method of claim 72, wherein the second agent stimulates a CD40 associated signal in the B cell.
- 74. The method of claim 73, wherein the second agent is a CD40 ligand.
- 75. The method of claim 66, further comprising contacting the B cells with T cells.
- 76. The method of claim 75, further comprising contacting the B cells with at least one antigen.
- 77. The method of claim 65, wherein the agent inhibits a CD100 ligand-associated signal, such that a response by the B cell is inhibited.
- 78. The method of claim 77, wherein the agent interacts with CD100.
- 79. The method of claim 78, wherein the agent is an antibody to CD100.
- 80. The method of claim 77, wherein the agent interacts with a CD100 ligand.
- 81. The method of claim 80, wherein the agent is an inhibitory form of CD100.
- 82. The method of claim 65, wherein the B cell response is B cell aggregation.
- 83. The method of claim 65, wherein the B cell response is B cell differentiation.
- 84. The method of claim 83, wherein the B cells differentiate into plasma cells.
- 85. The method of claim 83, wherein the B cells differentiate to memory B cells.
- 86. The method of claim 65, wherein the B cell response is B cell viability.
- 87. The method of claim 65, wherein contacting the cells is in a subject, such that a response by the B cell is modulated in the subject.
- 88. The method of claim 87, wherein the agent stimulates a B cell response in a subject infected with a pathogen, such that elimination of the pathogen by the subject is enhanced.
- 89. The method of claim 87, wherein the agent stimulates a B cell response in a subject having a low grade lymphoma, such that the B cell differentiation in the subject is stimulated.
- 90. The method of claim 88, further comprising administering to the subject a second agent which stimulates a CD40-associated signal in the B cell.
- 91. The method of claim 87, wherein the agent inhibits a B cell response in an allergic subject, such that the B cell response by the subject to an allergen is inhibited.
- 92. The method of claim 87, wherein the agent inhibits a B cell response in a subject having a large cell lymphoma, such that differentiation of the B cell in the subject is inhibited.
- 93. A method for modulating an interaction between an immune cell and a nerve cell in a subject, comprising administering to a subject an agent which modulates a CD100 ligand-associated signal in the nerve cell, such that modulation of the interaction between the immune cell and the nerve cell in the subject occurs.
- 94. A method for modulating axonal growth of a neuron, comprising contacting the neuron with a modulating form of CD100, such that axonal growth is modulated.
- 95. A method for modulating a T cell response, comprising contacting the T cell with an agent which modulates a CD100 ligand-induced signal in the T cell, such that a response in the T cell is modulated.
- 96. The method of claim 95, wherein a T cell is contacted with an agent which stimulates a CD100 ligand-induced signal in the T cell, such that a response in the T cell is stimulated.
- 97. The method of claim 96, further comprising contacting the T cell with an agent which provides a primary activation signal to the T cell.
- 98. The method of claim 95, wherein the T cell is contacted with an agent which inhibits a CD100 ligand-induced signal in the T cell, such that a response in the T cell is inhibited.
GOVERNMENT FUNDING
[0001] Work described herein was supported under grants CA40216-11 and AI35225-03 awarded by the National Institutes of Health. The U.S. government therefore may have certain rights in this invention.