Synthetic peptides that inhibit binding of the collagen type II 261-273 epitope to rheumatoid arthritis-associated HLA-DR1 and-DR4 molecules and collagen-specific T-cell responses

Copolymer 1 [Cop 1, poly (Y, E, A, K)] is a random synthetic amino acid cop olymer effective in the treatment of relapsing forms of multiple sclerosis (MS), a disease chat is linked to HLA-DR2 (DRB1*1501). Another copolymer [p oly (Y, A, K)1 was also identified thar binds to rheumatoid arthritis (RA)- associated HLA-DR1 (DRB1*0101) or HLA-DR4 (DRB1*0401) molecules and inhibit s the response of HLA-DR1- and -DR4-restricted T cell clones to an immunodo minant epitope of collagen type II (CII) 261-273 (a candidate autoantigen i n RA). In the present: study various peptides have been synthesized based o n binding "motifs" of Cop 1 for HLA-DR1 and -DR4 molecules. Those peptides with K at P-1 or K at P8 were particularly effective as inhibitors of bindi ng of CII 261-273, of Cop 1 and of the influenza virus hemagglutinin peptid e 306-318 to these class II proteins. Moreover, several of them were also p otent inhibitors of the CII 261-273-reactive T cell clones. These Findings suggest that small peptides or their more stable derivatives may be able to substitute for copolymers in the treatment of RA, and by implication of MS . Human Immunology 61, 640-650 (2000). (C) American Society for Histocompat ibility and Immunogenetics, 2000. Published by Elsevier Science Inc.