COOPERATIVE ACTIVATION OF TCRS BY ENTEROTOXIN SUPERANTIGENS

Staphylococcus enterotoxin superantigens are potent T cell activators. To gain new insights into the mechanism of T cell activation induced by these superantigens, we investigated the recruitment of signaling m olecules in this process. Here, we show that enterotoxin superantigen activation can be transmitted to TCR-CD3 complexes that did not intera ct with their ligand, Indeed, by studying cells expressing two distinc t TCRs, we found that enterotoxin superantigens induced tyrosine phosp horylation of TCR zeta subunits, the recruitment and tyrosine phosphor ylation of the protein tyrosine kinase ZAP-70, and an increase in prot ein tyrosine kinase activity of both directly stimulated and unstimula ted TCR-CD3 complexes. As the involvement of unstimulated TCR-CD3 comp lexes in signal transduction would increase the number of signaling mo lecules and, therefore, the efficiency of T cell activation, these dat a provide a novel explanation for the ability of enterotoxin superanti gens to potently activate T lymphocytes.