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.
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Authors | S Weerth, T Berger, H Lassmann, C Linington |
Journal | Journal of neuroimmunology
(J Neuroimmunol)
Vol. 95
Issue 1-2
Pg. 157-64
(Mar 01 1999)
ISSN: 0165-5728 [Print] Netherlands |
PMID | 10229126
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal
- Epitopes
- Myelin-Associated Glycoprotein
- Peptide Fragments
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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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