Staphylococcal enterotoxin enhances the activation of rat encephalitogenic T cells by myelin basic protein

It is generally believed that the activation of autoreactive T cells is an essential step in the pathogenesis of autoimmune diseases; however, autologous antigens are often weak immunogens and their detectable levels in vivo are much lower than required for T-cell activation. In experimental autoimmune encephalomyelitis, encephalitogenic T cells specific for myelin basic protein (MBP) react weakly to autologous rat myelin basic protein (RBP) but strongly to guinea pig-derived basic protein, even though both ligands possess the essential epitope (MBP(68-88)). Here we demonstrate that RBP is converted to a strong immunogen in the presence of a small dose of bacterial superantigen, staphylococcal enterotoxin E (SEE). The enhancing effect of SEE on the rat protein was apparent with all encephalitogenic T-cell lines examined in this study, including those not responding to RBP alone. It depended, moreover, on the simultaneous presence of RBP and SEE; delaying the addition of SEE for 8-12 h greatly decreased the potency of RBP. None of a series of major cytokines was able to replace SEE as an enhancer. Our results indicate that two T ligands, one a bacterial superantigen, can interact to enhance the activation of autoreactive T cells. This observation has implications for the involvement of bacterial and viral infections in the pathogenesis of multiple sclerosis.