Copolymer 1 inhibits chronic relapsing experimental allergic encephalomyelitis induced by proteolipid protein (PLP) peptides in mice and interferes with PLP-specific T cell responses

Abstract

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.