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

J Neuroimmunol. 1996 Feb;64(2):209-17. doi: 10.1016/0165-5728(95)00180-8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigen Presentation / drug effects
  • Antigen-Presenting Cells / drug effects
  • Antigen-Presenting Cells / immunology
  • Binding, Competitive
  • Chronic Disease
  • Clone Cells
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Glatiramer Acetate
  • Immunosuppressive Agents / pharmacology*
  • Lymph Nodes / drug effects
  • Lymph Nodes / immunology
  • Mice
  • Mice, Inbred Strains
  • Molecular Sequence Data
  • Myelin Proteolipid Protein / antagonists & inhibitors*
  • Peptides / pharmacology*
  • Protein Binding / drug effects
  • Recurrence
  • Spinal Cord / immunology
  • Spleen / drug effects
  • Spleen / immunology
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology

Substances

  • Immunosuppressive Agents
  • Myelin Proteolipid Protein
  • Peptides
  • Glatiramer Acetate