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International Immunology, Vol. 11, No. 5, 635-641, May 1999
© 1999 Japanese Society for Immunology

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

Masha Fridkis-Hareli, Rina Aharoni1, Dvora Teitelbaum1, Ruth Arnon1, Michael Sela1 and Jack L. Strominger

Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA
1 Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel

Correspondence to: J. L. Strominger

Copolymer 1 [Cop 1, poly(Y,E,A,K)] is a random synthetic amino acid copolymer of L-tyrosine, L-glutamic acid, L-alanine and L-lysine, 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 purified human HLA-DR molecules within the peptide-binding groove. In the present study the binding of copolymers composed of three of the four amino acids found in poly(Y,E,A,K) to purified class II MHC molecules was examined. Poly(Y,A,K) and poly(Y,E,A,K) bound to purified human 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 binders 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) and 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.

Keywords: amino acid copolymers, HLA-DR, multiple sclerosis

Transmitting editor: L. Steinman


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