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 Vβ chains, causing the activation and deletion of most T cells expressing products of determined Vβ gene families [1–4], The fact that superanti‐gens 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‐Vβ 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 Vβ products. In addition, therapeutic interventions targeted to Vβ gene products that are not specific for self‐superantigens are successful in preventing disease development. The lack of correlation between superantigen‐related Vβ 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.