Synthetic copolymer 1 inhibits human T-cell lines specific for myelin basic protein.
Copolymer 1 (Cop 1) is a synthetic basic random copolymer of amino acids that has been shown to be effective in suppression of experimental allergic encephalomyelitis and has been proposed as a candidate drug for multiple sclerosis. Cop 1 is immunologically cross reactive with myelin basic protein (BP) and was shown to inhibit murine BP-specific T-cell lines of various H-2 restrictions. In the present study these findings were extended to include human T-cell lines. Cop 1 competitively inhibited the proliferative responses and interleukin 2 secretion of six BP-specific T-cell lines and 13 clones with several DR restrictions and epitope specificities. Conversely, BP inhibited--albeit to a lesser extent--the response of all the Cop 1-specific T-cell lines and clones, irrespective of their DR restrictions. Another random copolymer of tyrosine, glutamic acid, and alanine, denoted TGA, had no effect on these lines. Neither Cop 1 nor BP inhibited the response of lines and clones specific for purified protein derivative. Cop 1 and BP exerted their cross-inhibitory effects only in the presence of antigen-presenting cells. These results suggest that Cop 1 can compete with BP for the binding to human major histocompatibility complex molecules. In view of recent studies implicating BP reactivity in multiple sclerosis, these findings suggest a possible mechanism for the beneficial effect of Cop 1 in this disease.
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
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D
Teitelbaum
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R
Milo
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R
Arnon
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Sela
D000938:Antigen-Presenting Cells / Q000276:immunology; D001667:Binding, Competitive; D002999:Clone Cells; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D009103:Multiple Sclerosis / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D006684:HLA-DR Antigens; D004676:Myelin Basic Protein; D010455:Peptides; C021759:(T,G)-A-L