ltered collagen II peptides inhibited T-cell activation in rheumatoid arthritis

It has been reported that collagen II (CII)-derived peptide induced T-cell activation via its amino acids responsible for T-cell receptor (TCR) ecognition. In this study, three altered CII263–272 peptide ligands (APL) containing multiple substitutions of TCR contact residues were ynthesized. Their roles in inhibition of T-cell activation were evaluated in peripheral blood lymphocytes (PBL) of rheumatoid arthritis (RA) in itro. It was shown that 41% (25/61) of RA patients were responsive to the wild-type antigenic CII263–272. In contrast, marginal or silent T-cell esponses to the three APLs were found, accompanied by inhibitory effects on secretion of Th1 type cytokines and expression of cell surface arkers, CD69 and CD25. In addition, T-cell activation induced by the wild-type antigenic CII263–272 was inhibited by all the three APLs in a ose-dependent manner. It is demonstrated that APLs with substitutions of TCR contact residues are capable of down-regulating T-cell responses n PBLs of RA, suggesting that the CII-derived APLs are potentially therapeutic in RA. 2005 Elsevier Inc. All rights reserved.