SUPERANTIGENS INDUCE PRIMARY T-CELL RESPONSES TO SOLUBLE AUTOANTIGENS BY A NON-V-BETA-SPECIFIC MECHANISM OF BYSTANDER ACTIVATION

Superantigens have been suggested to act as powerful TCR V beta-specific inducers of T cell reactivity in autoimmune diseases, We have investigated the capacity of staphylococcal enterotoxins (SE) to prime autoreactive T cell responses in naive animals in the Lewis rat model of experimental autoimmune encephalomyelitis (EAE), where myelin basic protein (MBP)-specific CD4(+) effector T cells express almost exclusively V beta 8.2 TCR elements, By taking advantage of the reactivity of V beta 8.2(+) MBP-specific T cells to SEE but not to other SEs in vitro, we estimated the potential of different SEs (SEA, SEB, and SEE) to induce a primary T cell response to soluble MBP in vivo, Upon immunization of naive rats with soluble MBP alone or MBP and SEB (which is only a very weak superantigen for rat T cells), no MBP-responses could be retrieved, Similarly, when coimmunizing naive rats with MBP and V beta 8.2-activating SEE, no autoreactivity was inducible, By contrast, coimmunization of animals with soluble MBP and the superantigen SEA that is strongly activating various T cell subpopulations in Lewis rats but not V beta 8.2(+) (i,e., potentially MBP reactive) T cells led to a significant primary MBP-specific T cell autoreactivity. These SEA-induced MBP-reactive T cells expressed V beta 8.2 TCRs at levels similar to those seen in autoreactive T cells conventionally induced by immunization with MBP administered in complete Freund's adjuvant (CFA) and could induce disease in a transfer model of EAE, Thus, our results are consistent with the notion that superantigens are able to induce primary T cell responses to soluble autoantigens by a non-V beta specific mechanism of bystander priming. (C) 1995 Academic Press,Inc.