Superantigens Induce Primary T Cell Responses to Soluble Autoantigens by a Non-Vβ-Specific Mechanism of Bystander Activation

Superantigens have been suggested to act as powerful TCR Vβ-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 Vβ8.2 TCR elements. By taking advantage of the reactivity of Vβ8.21 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 Vβ8.2-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 Lowis rats but not Vβ8.2+ (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 Vβ8.2 TCRs at levels similar to those seen in autoreactive T cells conventionally induced by immunization with MBP administered in complete Freundʹs 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-Vβ specific mechanism of bystander priming.