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Encephalitogenic and neuritogenic T cell responses to the myelin-associated glycoprotein (MAG) in the Lewis rat.

Abstract
Autoimmune responses to the myelin-associated glycoprotein (MAG) are implicated in the immunopathogenesis of both multiple sclerosis (MS) and certain peripheral neuropathies. In this study we demonstrate that T cell responses to defined epitopes of MAG mediate a pathological inflammatory response in the nervous system of the Lewis rat. Peptide-specific T cells were generated against four different MAG epitopes, three of which are common to both L- and S-isoforms of MAG (amino acid (a.a.) sequence: 20-34, 124-137, 354-377) whilst the fourth epitope (a.a. sequence: 570-582) is located in the C-terminal sequence of S-MAG. The adoptive transfer of T cells specific for these epitopes initiated a mild but dose-dependent inflammatory response in the central nervous system (CNS) of naive recipients. Clinical disease was only observed in those animals injected with T cells specific for the a.a. sequence 20-34 (MP1.1), which also initiated an inflammatory response in the peripheral nervous system (PNS). Co-transfer of MP1.1 (a.a. sequence 20-34)-specific T cells with the myelin oligodendrocyte glycoprotein (MOG)-specific monoclonal antibody 8-18C5 enhanced disease severity and induced widespread demyelination in the CNS. In contrast, co-transfer of T cells with the MAG-specific mAb 513 failed to induce demyelination, but had a moderate effect on the local inflammatory response. The ability of MAG to initiate an autoaggressive T cell response in the Lewis rat supports the concept that MAG-specific autoimmune responses may play a role in the pathogenesis of immune mediated diseases of the nervous system in man.
AuthorsS Weerth, T Berger, H Lassmann, C Linington
JournalJournal of neuroimmunology (J Neuroimmunol) Vol. 95 Issue 1-2 Pg. 157-64 (Mar 01 1999) ISSN: 0165-5728 [Print] Netherlands
PMID10229126 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Monoclonal
  • Epitopes
  • Myelin-Associated Glycoprotein
  • Peptide Fragments
Topics
  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal
  • Blood-Brain Barrier (immunology)
  • Brain Chemistry (immunology)
  • Encephalomyelitis, Autoimmune, Experimental (immunology)
  • Epitopes (immunology)
  • Molecular Sequence Data
  • Multiple Sclerosis (immunology)
  • Myelin-Associated Glycoprotein (genetics, immunology)
  • Neuritis (immunology)
  • Peptide Fragments (genetics, immunology)
  • Rats
  • Rats, Inbred Lew
  • Spinal Cord (chemistry, immunology)
  • Spinal Nerve Roots (chemistry, immunology)
  • T-Lymphocytes (chemistry, immunology)

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