Methods for inhibiting immune complex formation in a subject
Polypeptides and other compounds that can bind specifically to the C H 2-C H 3 cleft of an immunoglobulin molecule, and methods for using such polypeptides and compounds to inhibit Fc-mediated immune complex formation, are described.
1. A method for inhibiting immune complex formation in a subject, said method comprising administering to said subject a composition comprising a purified polypeptide, said polypeptide comprising the amino acid sequence Cys-Ala-Xaa-His-Leu-Gly-Glu-Leu-Val-Trp-Cys-Thr (SEQ ID NO:8), wherein Xaa is Arg, Trp, Tyr, or Phe.
2. The method of claim 1 , wherein said immune complex formation is associated with rheumatoid arthritis.
3. The method of claim 2 , further comprising the step of monitoring said subject for clinical or molecular characteristics of rheumatoid arthritis.
4. The method of claim 1 , wherein said polypeptide further comprises a terminal stabilizing group.
5. The method of claim 4 , wherein said terminal stabilizing group is at the amino terminus of said polypeptide and is a tripeptide having the amino acid sequence Xaa-Pro-Pro, wherein Xaa is any amino acid.
6. The method of claim 5 , wherein Xaa is Ala.
7. The method of claim 4 , wherein said terminal stabilizing group is at the carboxy terminus of said polypeptide and is a tripeptide having the amino acid sequence Pro-Pro-Xaa, wherein Xaa is any amino acid.
8. The method of claim 7 , wherein Xaa is Ala.
9. The method of claim 4 , wherein said terminal stabilizing group is a small stable protein.
10. The method of claim 9 , wherein said small stable protein comprises a four-helix bundle topology.
11. The method of claim 9 , wherein said small stable protein is Rop.
12. The method of claim 1 , wherein said polypeptide further comprises an additional amino acid at the amino terminus of said amino acid sequence.
13. The method of claim 12 , wherein said additional amino acid is any amino acid other than Cys.
14. The method of claim 12 , wherein said additional amino acid is Asp.
15. The method of claim 1 , wherein said polypeptide has a length of about 10 to about 50 amino acids.
16. The method of claim 1 , wherein said polypeptide comprises the amino acid sequence Asp-Cys-Ala-Trp-His-Leu-Gly-Glu-Leu-Val-Trp-Cys-Thr (SEQ ID NO:2).
17. The method of claim 1 , wherein said polypeptide comprises the amino acid sequence Trp-Glu-Ala-Asp-Cys-Ala-Xaa-His-Leu-Gly-Glu-Leu-Val-Trp-Cys-Thr-Lys-Val-Glu-Glu (SEQ ID NO:32).
18. The method of claim 1 , wherein said polypeptide comprises the amino acid sequence Ala-Pro-Pro-Asp-Cys-Ala-Trp-His-Leu-Gly-Glu-Leu-Val-Trp-Cys-Thr (SEQ ID NO:47).