Molecular mimicry and multiple sclerosis — a possible role for degenerate T cell recognition in the induction of autoimmune responses
Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system. The etiology is unknown, but several lines of evidence support the hypothesis that the pathogenesis is mediated by autoreactive T lymphocytes. Molecular mimicry has been proposed as a possible mechanism for the development of an autoimmune response to myelin antigens. According to this model, an immune reaction to self antigens could be initiated by T cells that cross-react with infectious agents that “mimic” the autoantigen, i.e. they share immunologic epitopes. It was previously thought that, in order for a cross-reaction of T cells to two different antigens to occur, a substantial amino acid sequence homology between the two antigens was required. More recent studies on the basic mechanisms of T cell antigen recognition have shown that, at least for some T cell clones, antigen recognition is more “degenerate” and sequence homology is not required for crossreactivity to occur. This article reviews the relevance of these recent advances in basic T cell receptor immunology to the occurrence of autoimmunity in the central nervous system.
KeywordsMultiple Sclerosis Experimental Autoimmune Encephalomyelitis Myelin Basic Protein Antigenic Peptide Experimental Allergic Encephalomyelitis
Unable to display preview. Download preview PDF.
- Ebers GC, Kukay K, Bulman DE, Sadovnick AD, Rice G, Anderson C, Armstrong H, Cousin K, Bell RB, Hader W, Paty DW, Hashimoto S, Oger J, Duquette P, Warren S, Gray T, O’Connor P, Nath A, Auty A, Metz L, Francis G, Paulseth JE, Murray TJ, Pryse-Phillips W, Risch N, et al (1996) A full genome search in multiple sclerosis. Nat Genet 13: 472–476.PubMedCrossRefGoogle Scholar
- Haines JL, Ter-Minassian M, Bazyk A, Gusella JF, Kim DJ, Terwedow H, Pericak-Vance MA, Rimmler JB, Haynes CS, Roses AD, Lee A, Shaner B, Menold M, Seboun E, Fitoussi RP, Gartioux C, Reyes C, Ribierre F, Gyapay G, Weissenbach J, Hauser SL, Goodkin DE, Lincoln R, Usuku K, Oksenberg JR et al (1996) A complete genomic screen for multiple sclerosis underscores a role for the major histocompatability complex. Nat Genet 13: 469–471.PubMedCrossRefGoogle Scholar
- Kurtzke J (1985) Epidemiology of multiple sclerosis. In: Vinken PJ, Bruyn GB, Klawans HL, et al (eds) Handbook of clinical neurology, vol 3: Demyelinating diseases. Elsevier, Amsterdam, pp 259–287.Google Scholar
- Martin R, McFarland HF (1997) Immunology of multiple sclerosis and experimental allergic encephalomyelitis. In: Raine CS, McFarland HF, Tourtellotte WW (eds) Multiple sclerosis: clinical and pathogenetic basis. Chapman Hall, London, pp 221–242.Google Scholar
- Raine CS (1997) The lesion in multiple sclerosis and chronic relapsing experimental allergic encephalomyelitis: a structural comparison. In: Raine CS, McFarland HF, Tourtellotte WW (eds) Multiple sclerosis: clinical and pathogenetic basis. Chapman Hall, London, pp 243–286.Google Scholar
- Remlinger J (1905) Accidents paralytiques au cours du traitment antirabique. Ann Inst Pasteur 19: 625–646.Google Scholar
- Schlüsener H, Wekerle H (1985) Autoaggressive T lymphocyte lines recognize the encephalitogenic region of myelin basic protein; in vitro selection from unprimed rat T lymphocyte populations. J Immunol 135: 3128–3133.Google Scholar