Promiscuous binding of synthetic copolymer 1 to purified HLA-DR molecules.
Article Details
- CitationCopy to clipboard
Fridkis-Hareli M, Strominger JL
Promiscuous binding of synthetic copolymer 1 to purified HLA-DR molecules.
J Immunol. 1998 May 1;160(9):4386-97.
- PubMed ID
- 9574543 [ View in PubMed]
- 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.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Glatiramer HLA class II histocompatibility antigen, DRB1-1 beta chain Protein Humans UnknownBinderDetails Glatiramer HLA class II histocompatibility antigen, DRB1-15 beta chain Protein Humans UnknownBinderDetails Glatiramer HLA class II histocompatibility antigen, DRB1-4 beta chain Protein Humans UnknownBinderDetails