Promiscuous binding of synthetic copolymer 1 to purified HLA-DR molecules

M Fridkis-Hareli, JL Strominger - The Journal of Immunology, 1998 - journals.aai.org
M Fridkis-Hareli, JL Strominger
The Journal of Immunology, 1998journals.aai.org
Abstract 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 …
Abstract
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.
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