Synthetic peptides that inhibit binding of the myelin basic protein 85-99 epitope to multiple sclerosis-associated HLA-DR2 molecules and MBP-specificT-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 that is linked to HLA-DR2 (DRB1*1501). In the present study various peptides, synthesized according to the binding motifs for both the immunodominant epitope of myelin basic protein (MBP) 85-99, a candidate au toantigen in MS, and Cop 1, differentially inhibited binding of these antig ens to disease-associated HLA-DR2 (DRBI*1501) molecules. In particular, two peptides with residue K at position P-1, as referred to MBP 85-99, inhibit ed effectively the binding of both biotinylated MBP 85-99 and Cop 1 to HLA- DR2 molecules as well as IL-2 production by two MBP-specific HLA-DR2-restri cted T-cell clones. These findings suggest the possible utility of these co mpounds or their more stable derivatives in treatment of MS. Human Immunolo gy 62, 753-763 (2001). (C) American Society for Histocompatibility and Immu nogenetics, 2001. Published by Elsevier Science Inc.