The inhibitory effect of altered collagen II peptide on HLA-DRB1-restricted T-cell activation.

It has been known that rheumatoid arthritis (RA)-associated antigenic peptides CII263-272 are coupled with human leucocyte antigen (HLA)-DRB1 and recognized by T-cell receptor (TCR), which in turn induced T-cell proliferation and pathogenesis of RA. Non-T-cell-stimulating type II collagen (CII) peptides might be generated by removing the amino acids responsible for TCR contact and keeping the HLA-DR-binding residues intact. In this study, a panel of altered CII peptides (APs) with consecutive or single substitutions of the TCR-contacting residues were synthesized. Through peptide binding and T-cell activation assays, we demonstrated that altered CII263-272 peptides with substitution of the TCR-contacting residues did not or barely induced T-cell activation; one of the best non-T-cell-stimulating peptide AP268-270 inhibited the binding of wild-type CII263-272 to HLA-DR1 and T-cell activation triggered by wild-type CII263-272 and HA306-318 in a dose-response manner. These data suggest that removal of the TCR-contacting residues of CII263-272 leads to HLA-DRB1 binding and low T-cell-stimulating peptides, which could potentially inhibit the T-cell response induced by HLA-DRB1-binding antigenic peptides.