Copolymer-1-induced inhibition of antigen-specific T cell activation: interference with antigen presentation.
Copolymer-1 (Cop-1) has been shown to inhibit in vivo development of experimental allergic encephalomyelitis (EAE) in animals and has been reported to have some therapeutic benefit in relapsing/remitting multiple sclerosis (MS). The mechanism by which Cop-1 acts in vivo is not known. The present study demonstrates that Cop-1 inhibits the in vitro response of several antigen-specific murine T cell hybridomas restricted to I-A, and to a lesser extent, I-E. The ability of human myelin basic protein (MBP)-specific T cell lines (TCL) to lyse targets in the context of three HLA-DR types associated with MS was also impaired by Cop-1. The results suggest that the observed inhibition was due to competition between Cop-1 and nominal antigen for the class II major histocompatibility complex (MHC) peptide binding site.
Neuroimmunology Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892.
M K
MK
Racke
R
R
Martin
H
H
McFarland
R B
RB
Fritz
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology; D001667:Binding, Competitive; D002460:Cell Line; D000939:Epitopes; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology; D010455:Peptides / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects*
D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein; D010455:Peptides; C021759:(T,G)-A-L