Dissociation of autoaggression and self-superantigen reactivity.
Self-superantigens have been described as products of endogenous retroviruses of the mouse ('minor lymphocyte stimulating loci') that are capable of interacting without prior processing with conserved domains of TCR V beta chains, causing the activation and deletion of most T cells expressing products of determined V beta gene families [1-4]. The fact that superantigens activate a far higher percentage of T cells (1-20%) than conventional, peptidic antigens (< 0.1%) provides the methodological advantage that the degree of clonal deletion may be measured by the analysis of the TCR repertoire using appropriate anti-V beta antibodies. Although much information on the spatio-temporal organization of repertoire-purging has been gathered by virtue of self-superantigens, serious doubts exist as to the possibility that such structures serve as pathogenetically relevant autoantigens. Thus, certain inbred mice spontaneously develop autoimmune diseases, although they bear T-cell repertoires that appear to be purged from self-superantigen-reactive V beta products. In addition, therapeutic interventions targeted to V beta gene products that are not specific for self-superantigens are successful in preventing disease development. The lack of correlation between superantigen-related V beta deletions and autoimmune disease development is substantiated in further models of murine autoimmunity. Based on these observations, we formulate the hypothesis that self-superantigen-reactive T cells are not involved in the development of autoimmune diseases.
Gonzalo
J A
JA
de Alborán
I M
IM
Kroemer
G
G
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D001327:Autoimmune Diseases / Q000209:etiology*; D006801:Humans; D008177:Lupus Vulgaris / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D012190:Retroviridae / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000956:Antigens, Viral; D016693:Receptors, Antigen, T-Cell, alpha-beta