Binding of random copolymers of three amino acids to class II MHC molecules

Copolymer 1 [Cop 1, poly(Y,E,A,K)] is a random synthetic amino acid copolym er of L-tyrosine, L-glutamic acid, L-alanine and L-lysine, effective both i n suppression of experimental allergic encephalomyelitis and in the treatme nt of relapsing forms of multiple sclerosis. Cop 1 binds promiscuously and very efficiently to purified human HLA-DR molecules within the peptide-bind ing groove. In the present study the binding of copolymers composed of thre e of the four amino acids found in poly(Y,E,A,K) to purified class II MHC m olecules was examined. Poly(Y,A,K) and poly(Y,E,A,K) bound to purified huma n HLA-DR1 or -DR4 molecules with affinity higher than poly(Y,E,A), poly(E,A ,K) or poly(Y,E,K), whereas poly(Y,E,A,K) and poly(E,A,K) were the better b inders of HLA-DR2 molecules. On the other hand, poly(Y,E,A) and poly(Y,A,K) inhibited the binding of biotinylated poly(Y,E,A,K) to these molecules 10- fold more efficiently than poly(Y,E,K). Finally, poly(Y,E,A), poly(Y,A,K) a nd poly(E,A,K) were cross-reactive with poly(Y,E,A,K) using YEAK-specific T cell lines and clones of mouse or human origin.