Specific inhibition of the T-cell response to myelin basic protein by the synthetic copolymer Cop 1.

Abstract

Cop 1 is a synthetic basic random copolymer of L-alanine, L-glutamic acid, L-lysine, and L-tyrosine in a residue molar ratio of 6.0:1.9:4.7:1.0 and with a molecular weight of 21,000 which proved to be effective in specific suppression of experimental allergic encephalomyelitis and has been proposed as a candidate drug against multiple sclerosis. In the present study we further investigated the mechanism of Cop 1 suppressive activity and tested whether Cop 1 could inhibit the specific T-cell response to myelin basic protein (BP). Eight BP-specific T-cell lines and clones with various H-2 restrictions and antigenic specificities were used. The responses of all these lines and clones to BP, as followed by both cell proliferation and interleukin 2 secretion assays, were affected by Cop 1. For one line, a direct cross proliferation with Cop 1 was observed, whereas in the other seven lines and clones, Cop 1 specifically inhibited the responses to BP in a competitive dose-dependent manner. The inhibition of the response to BP is specific to Cop 1, as D-Cop 1 and another random acidic polymer, poly(Tyr,Glu,Ala) (TGA), both of which were previously demonstrated to be ineffective in suppression of experimental allergic encephalomyelitis, did not inhibit the response to BP. Furthermore, Cop 1 specifically inhibited only the response of the T-cell lines and clones to BP. It did not inhibit their response to the mitogen Con A, nor did it inhibit the responses of the purified protein derivative-specific T-cell line and clone. These results suggest that Cop 1 may be effective in suppression of experimental allergic encephalomyelitis, not only because of the selective stimulation of suppressor T cells, as we have previously demonstrated, but also by specific inhibition of BP-specific effector T cells.