The conventional CD4+ T cell response to staphylococcal enterotoxin B is modified by its superantigenic activity

Because of the massive cytokine response elicited by superantigen exposure, it has been suggested that superantigens may act as adjuvants to boost conventional antigen responses. However, most previous studies have shown that in vivo exposure to superantigen suppressed subsequent T cell responses. Here we analyzed the effect of the superantigen Staphylococcal enterotoxin B (SEB) on a concurrent CD4(+) immune response to a conventional antigen, an I-Ab-restricted epitope derived from the same protein (SEB127-142). Heat-inactivated SEB, which had lost all superantigenic activity, was capable of eliciting a strong CD4(+) proliferative T cell response to SEB127-142. In contrast, native SEB was relatively nonimmunogenic, even when administered in association with complete Freund's adjuvant. High doses of native SEB coadministered with heat-inactivated SEB had no effect on the peptide response. However, low doses of native SEB were able to strongly enhance the ability of inactive SEB to prime CD4(+) T cells to SEB127-142. Thus, SEB is not always immunosuppressive, and low doses may actually enhance a concurrent immune response. Also, the contribution of Vbeta8(+)/CD4(+) T cells to peptide reactivity was not affected by the presence of low doses of native SEB, suggesting that the enhanced reactivity was not a Vbeta-specific effect of SEB, but was cytokine-mediated.