Promiscuous binding of synthetic copolymer 1 to purified HLA-DR molecules.
Copolymer 1 (Cop 1) is a random synthetic amino acid copolymer of L-alanine, L-glutamic acid, L-lysine, and L-tyrosine, effective both in suppression of experimental allergic encephalomyelitis and in the treatment of relapsing forms of multiple sclerosis. Cop 1 binds promiscuously and very efficiently to living APCs of various HLA haplotypes. In the present study, a substantial part of the whole mixture of random polypeptides that compose Cop 1 was shown to bind to purified human HLA-DR1, DR2, and DR4 with high affinity in a temperature- and time (and, in the case of DR4, pH)-dependent manner, and was competitively inhibited by DR-restricted peptides, but not by peptide derivatives that bind with low affinity. Bacterial superantigens inhibited Cop 1 binding only at very high concentrations. The formation of the Cop 1-DR1 complex was also shown by SDS-PAGE. These findings represent the first direct evidence for interactions of Cop 1 with purified DR molecules, and suggest that its effectiveness in experimental allergic encephalomyelitis and multiple sclerosis may be directly related to its binding in the groove of HLA-DR proteins.
Fridkis-Hareli
M
M
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Strominger
J L
JL
D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology; D000068717:Glatiramer Acetate; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology; D010455:Peptides / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding
D006684:HLA-DR Antigens; D007166:Immunosuppressive Agents; D010455:Peptides; D000068717:Glatiramer Acetate