Copolymer 1 inhibits chronic relapsing experimental allergic encephalomyelitis induced by proteolipid protein (PLP) peptides in mice and interferes with PLP-specific T cell responses.
Copolymer 1 (Cop 1) is a synthetic amino acid copolymer effective in suppression of experimental allergic encephalomyelitis (EAE) and developed as a candidate drug for multiple sclerosis (MS). In the present study, we induced chronic relapsing (CR)-EAE in (SJL/J X BALB/c)F1 mice by either whole spinal cord homogenate or two synthetic peptides of proteolipid protein (PLP), p139-151 and p178-191. When Cop 1 was added to the encephalitogenic inoculum, mice were almost completely resistant to disease induction. T cell lines to p139-151 and p178-191 were specific to these peptides. Their antigen-specific responses were inhibited by Cop 1 in a dose-dependent manner, while their polyclonal response to the superantigen staphylococcal enterotoxin A (SEA) was not affected by Cop 1. Using biotinylated PLP derivatives, we demonstrated that the two PLP peptides bound to I-A(s) molecules, and that their binding was completely inhibited by unlabelled Cop 1. Furthermore, Cop 1 could displace the PLP peptides from the MHC binding site. These results support the potential of Cop 1 as a broad-spectrum drug for MS.
Teitelbaum
D
D
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Fridkis-Hareli
M
M
Arnon
R
R
Sela
M
M
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D001667:Binding, Competitive; D002908:Chronic Disease; D002999:Clone Cells; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology*; D000068717:Glatiramer Acetate; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D018991:Myelin Proteolipid Protein / Q000037:antagonists & inhibitors*; D010455:Peptides / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D012008:Recurrence; D013116:Spinal Cord / Q000276:immunology; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D007166:Immunosuppressive Agents; D018991:Myelin Proteolipid Protein; D010455:Peptides; D000068717:Glatiramer Acetate