Variant costimulatory polypeptides, nucleic acids encoding such polypeptides, and methods for using the polypeptides and nucleic acids to enhance a T cell response are provided herein.
1. A purified variant B7-H1 polypeptide which is a variant of a wild-type B7-H1 polypeptide, wherein said wild-type B7-H1 polypeptide binds to PD-1 and has the amino acid sequence set forth in SEQ ID NO:4, wherein said variant B7-H1 polypeptide comprises a substitution of the amino acid at position 67, 126, 37, 115, 124, 31, 49, 62, 98, or 129 of SEQ ID NO:4 and has binding affinity for PD-1 that is detectable by ELISA but is reduced by at least 50 percent as compared to the binding affinity of said wild-type B7H1 polypeptide for PD-1.
2. The purified variant B7-H1 polypeptide of claim 1 , comprising a substitution of the amino acid at position 67 of SEQ ID NO:4.
3. The purified variant B7-H1 polypeptide of claim 2 , wherein said substitution comprises replacing the amino acid at position 67 of SEQ ID NO:4 with an alanine residue.
4. The purified variant B7-H1 polypeptide of claim 1 , comprising a substitution of the amino acid at position 126 of SEQ ID NO:4.
5. The purified variant B7-H1 polypeptide of claim 4 , wherein said substitution comprises replacing the amino acid at position 126 of SEQ ID NO:4 with an alanine residue.
6. The purified variant B7-H1 polypeptide of claim 1 , comprising a substitution of the amino acid at position 37 of SEQ ID NO:4.
7. The purified variant B7-H1 polypeptide of claim 6 , wherein said substitution comprises replacing the amino acid at position 37 of SEQ ID NO:4 with a tyrosine residue.
8. The purified variant B7-H1 polypeptide of claim 1 , comprising a substitution of the amino acid at position 115 of SEQ ID NO:4.
9. The purified variant B7-H1 polypeptide of claim 8 , wherein said substitution comprises replacing the amino acid at position 115 of SEQ ID NO:4 with an alanine residue.
10. The purified variant B7-H1 polypeptide of claim 1 , comprising a substitution of the amino acid at position 124 of SEQ ID NO:4.
11. The purified variant B7-H1 polypeptide of claim 10 , wherein said substitution comprises replacing the amino acid at position 124 of SEQ ID NO:4 with a serine residue.
12. A polypeptide fragment of murine B7-H1 (SEQ ID NO:4) which comprises a variant at position 69 or 113 with respect to the sequence set forth in SEQ ID NO:4 and which inhibits binding of murine B7-H1 to murine PD-1, said polypeptide fragment comprising 259 to 271 amino acid residues and having Thr-290 of SEQ ID NO:4 at the carboxy terminal end.
13. A method of inhibiting the interaction between PD-1 and B7-H1, said method comprising contacting a PD-1 polypeptide with the polypeptide fragment of claim 12 .
14. The method of claim 13 , wherein said PD-1 is in vitro.
15. The method of claim 13 , wherein said PD-1 is in a mammal.
16. The method of claim 15 , wherein said method comprises administering the polypeptide fragment to the mammal.
17. The method of claim 15 , wherein said mammal is a human.
18. The purified variant B7-H1 polypeptide of claim 1 , comprising a substitution of the amino acid at position 31 of SEQ ID NO:4.
19. The purified variant B7-H1 polypeptide of claim 18 , wherein said substitution comprises replacing the amino acid at position 31 of SEQ ID NO:4 with a serine residue.
20. The purified variant B7-H1 polypeptide of claim 1 , comprising a substitution of the amino acid at position 49 of SEQ ID NO:4.
21. The purified variant B7-H1 polypeptide of claim 20 , wherein said substitution comprises replacing the amino acid at position 49 of SEQ ID NO:4 with a serine residue.
22. The purified variant B7-H1 polypeptide of claim 1 , comprising a substitution of the amino acid at position 62 of SEQ ID NO:4.
23. The purified variant B7-H1 polypeptide of claim 22 , wherein said substitution comprises replacing the amino acid at position 62 of SEQ ID NO:4 with a serine residue.
24. The purified variant B7-H1 polypeptide of claim 1 , comprising a substitution of the amino acid at position 98 of SEQ ID NO:4.
25. The purified variant B7-H1 polypeptide of claim 24 , wherein said substitution comprises replacing the amino acid at position 98 of SEQ ID NO:4 with a phenylalanine residue.
26. The purified variant B7-H1 polypeptide of claim 1 , comprising a substitution of the amino acid at position 129 of SEQ ID NO:4.
27. The purified variant B7-H1 polypeptide of claim 26 , wherein said substitution comprises replacing the amino acid at position 129 of SEQ ID NO:4 with a serine residue.