Synthetic amino acid copolymers that bind to HLA-DR proteins and inhibit type II collagen-reactive T cell clones.
Copolymer 1 [poly(Y,E,A,K)] is a random synthetic amino acid copolymer of L-tyrosine, L-glutamic acid, L-alanine, and L-lysine that is effective both in suppression of experimental allergic encephalomyelitis and in the treatment of relapsing forms of multiple sclerosis. Copolymer 1 binds promiscuously and very efficiently to purified HLA-DR molecules within the peptide-binding groove. In the present study, YEAK and YEAK-related copolymers and type II collagen (CII) peptide 261-273, a candidate autoantigen in rheumatoid arthritis (RA), competed for binding to RA-associated HLA-DR molecules encoded by DRB1*0101 and DRB1*0401. Moreover, these copolymers (particularly YEAK, YAK, and YEK) inhibited the response of DR1- and DR4-restricted T cell clones to the CII epitope 261-273 by >50%. This direct evidence both for competitive interactions of these copolymers and CII peptide with RA-associated HLA-DR molecules and for inhibition of CII-specific T cell responses suggests that these compounds should be evaluated in animal models for rheumatoid arthritis.
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
M
M
Fridkis-Hareli
E F
EF
Rosloniec
L
L
Fugger
J L
JL
Strominger
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D002999:Clone Cells; D003094:Collagen / Q000276:immunology*; D004330:Drosophila; D000939:Epitopes / Q000378:metabolism; D006684:HLA-DR Antigens / Q000378:metabolism*; D011108:Polymers; D011994:Recombinant Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D000596:Amino Acids; D000939:Epitopes; D006684:HLA-DR Antigens; D011108:Polymers; D011994:Recombinant Proteins; D003094:Collagen