A triple altered collagen II peptide with consecutive substitutions of TCR contacting residues inhibits collagen-induced arthritis.

摘要

The collagen type II (CII) 263-272 peptide is a predominant T and B cell antigenic peptide in rheumatoid arthritis. Crystallographic data showed that 263F and 264K of CII263-272 are mainly responsible for binding with HLA-DR, and that 267Q and 270K were the major T cell Teceptor (TCR)-contact residues. We have shown that the CII altered peptide ligand JAPL) with individual or consecutive substitutions of the TCR-contact amino acids could inhibit T cell activation induced by wild-type CII peptide in the context of HIA-DRB1, among which the most potent T cell activation suppressor is sub268-270, in which the amino acids of wild-type CII263-272 at positions 268, 269 and 270 were substituted with glycine or alanine (FKGEQAGAGE, substitutions underlined). Collagen-induced arthritis (CIA) is induced by wild-type CII in susceptible rodent strains. It has been regarded as the best rheumatoid arthritis model.