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 supp ort the hypothesis that the pathogenesis is mediated by autoreactive T lymp hocytes. Molecular mimicry has been proposed as a possible mechanism for th e development of an autoimmune response to myelin antigens. According to th is 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 subst antial amino acid sequence homology between the two antigens was required. More recent studies on the basic mechanisms of T cell antigen recognition h ave shown that, at least for some T cell clones, antigen recognition is mor e "degenerate" and sequence homology is not required for crossreactivity to occur. This article reviews the relevance of these recent advances in basi c T cell receptor immunology to the occurrence of autoimmunity in the centr al nervous system.