Human collagen II peptide 256-271 preferentially binds to HLA-DR moleculesassociated with susceptibility to rheumatoid arthritis

The binding ability of 23 overlapping peptides, all derived from the CB11 f ragment of CII, was tested on several HLA-DR molecules associated or not wi th disease susceptibility. These experiments were performed on a variety of cells expressing different HLA-DR molecules, using both indirect and direc t binding assays. The CII (256-271) fragment was shown to bind to a restric ted population among which the HLA-DR molecules associated with susceptibil ity to rheumatoid arthritis. The results also clearly indicate that the bin ding specificity of CII (256-271), among the DR4 molecules, is controlled b y the nature of the HLA-DR molecule P-chain residues 71 and 74, residues pr eviously shown by X-ray crystallography to be involved in the HLA-DR/peptid e interaction. The human CII (256-271) peptide is thus likely to play a rol e in the disease process.