Encephalitogenic and neuritogenic T cell responses to the myelin-associated glycoprotein (MAG) in the Lewis rat.
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.
Weerth
S
S
Department of Neuroimmunology, Max-Planck Institute of Neurobiology, Martinsried, Germany. weerth@genectr.hunter.cuny.edu
Berger
T
T
Lassmann
H
H
Linington
C
C
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D001812:Blood-Brain Barrier / Q000276:immunology; D001923:Brain Chemistry / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology; D018992:Myelin-Associated Glycoprotein / Q000235:genetics / Q000276:immunology*; D009443:Neuritis / Q000276:immunology; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000737:chemistry / Q000276:immunology; D013126:Spinal Nerve Roots / Q000737:chemistry / Q000276:immunology; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D018992:Myelin-Associated Glycoprotein; D010446:Peptide Fragments