Compositions and methods for modulating lymphocyte activity
The present invention provides a novel lymphocyte inhibitory receptor termed BTLA which is expressed on both T and B cells, and identifies HVEM as interacting with BTLA. Methods and compositions for modulating BTLA-mediated signaling and interfering with the interaction of BTLA and HVEM for therapeutic, diagnostic and research purposes are also provided.
1. An isolated antibody that binds to a unique epitope on a BTLA protein, wherein the antibody binds to the amino acid sequence set forth in SEQ ID NO:6.
2. The antibody of claim 1 , wherein the BTLA protein is capable of inhibiting lymphocyte activity.
3. The antibody of claim 2 , wherein the lymphocyte activity is lymphocyte proliferation.
4. The antibody of claim 1 , wherein the BTLA protein is capable of inhibiting T cell activity.
5. The antibody of claim 4 , wherein the T cell activity is T cell proliferation.
6. The antibody of claim 1 , wherein the BTLA protein is capable of inhibiting CD4+ T cell activity.
7. The antibody of claim 6 , wherein the CD4+ T cell activity is CD4+ T cell proliferation.
8. The antibody of claim 1 , wherein the BTLA protein is capable of inhibiting Th1 cell activity.
9. The antibody of claim 8 , wherein the Th1 cell activity is Th1 cell proliferation.
10. The antibody of claim 1 , wherein the BTLA protein is capable of inducible association with SHP-2 in T cells.
11. The antibody of claim 1 , wherein the BTLA protein is capable of inducible association with SHP-2 in CD4+ T cells.
12. The antibody of claim 1 , wherein the BTLA protein is capable of inducible association with SHP-2 in Th1 cells.
13. An isolated antibody that binds to a unique epitope in an extracellular domain of a BTLA protein, wherein the antibody binds to the amino acid sequence set forth in SEQ ID NO:6.
14. The antibody of claim 13 , wherein the BTLA protein is capable of inhibiting lymphocyte activity.
15. The antibody of claim 14 , wherein the lymphocyte activity is lymphocyte proliferation.
16. The antibody of claim 13 , wherein the BTLA protein is capable of inhibiting T cell activity.
17. The antibody of claim 16 , wherein the T cell activity is T cell proliferation.
18. The antibody of claim 13 , wherein the BTLA protein is capable of inhibiting CD4+ T cell activity.
19. The antibody of claim 18 , wherein the CD4+ T cell activity is CD4+ T cell proliferation.
20. The antibody of claim 13 , wherein the BTLA protein is capable of inhibiting Th1 cell activity.
21. The antibody of claim 20 , wherein the Th1 cell activity is Th1 cell proliferation.
22. The antibody of claim 13 , wherein the BTLA protein is capable of inducible association with SHP-2 in T cells.
23. The antibody of claim 13 , wherein the BTLA protein is capable of inducible association with SHP-2 in CD4+ T cells.
24. The antibody of claim 13 , wherein the BTLA protein is capable of inducible association with SHP-2 in Th1 cells.
25. An isolated antibody that specifically binds to a BTLA protein having an amino acid sequence set forth in SEQ ID NO:6.
26. The antibody of claim 25 , wherein the BTLA protein is capable of inhibiting lymphocyte activity.
27. The antibody of claim 26 , wherein the lymphocyte activity is lymphocyte proliferation.
28. The antibody of claim 25 , wherein the BTLA protein is capable of inhibiting T cell activity.
29. The antibody of claim 28 , wherein the T cell activity is T cell proliferation.
30. The antibody of claim 26 , wherein the BTLA protein is capable of inhibiting CD4+ T cell activity.
31. The antibody of claim 30 , wherein the CD4+ T cell activity is CD4+ T cell proliferation.
32. The antibody of claim 25 , wherein the BTLA protein is capable of inhibiting Th1 cell activity.
33. The antibody of claim 32 , wherein the Th1 cell activity is Th1 cell proliferation.
34. The antibody of claim 25 , wherein the BTLA protein is capable of inducible association with SHP-2 in T cells.
35. The antibody of claim 25 , wherein the BTLA protein is capable of inducible association with SHP-2 in CD4+ T cells.
36. The antibody of claim 25 , wherein the BTLA protein is capable of inducible association with SHP-2 in Th1 cells.
37. An isolated antibody that specifically binds to a BTLA protein having an amino acid sequence set forth in SEQ ID NO:6, wherein the antibody binds to the extracellular domain of the protein.
38. The antibody of claim 36 , wherein the BTLA protein is capable of inhibiting lymphocyte activity.
39. The antibody of claim 37 , wherein the lymphocyte activity is lymphocyte proliferation.
40. The antibody of claim 36 , wherein the BTLA protein is capable of inhibiting T cell activity.
41. The antibody of claim 40 , wherein the T cell activity is T cell proliferation.
42. The antibody of claim 36 , wherein the BTLA protein is capable of inhibiting CD4+ T cell activity.
43. The antibody of claim 42 , wherein the CD4+ T cell activity is CD4+ T cell proliferation.
44. The antibody of claim 36 , wherein the BTLA protein is capable of inhibiting Th1 cell activity.
45. The antibody of claim 44 , wherein the Th1 cell activity is Th1 cell proliferation.
46. The antibody of claim 36 , wherein the BTLA protein is capable of inducible association with SHP-2 in T cells.
47. The antibody of claim 36 , wherein the BTLA protein is capable of inducible association with SHP-2 in CD4+ T cells.
48. The antibody of claim 36 , wherein the BTLA protein is capable of inducible association with SHP-2 in Th1 cells.