Crosslinked Staphylococcal Enterotoxin B Stimulates CD8 + T Cells Only in the Presence of Unlinked Costimulator Signals

Abstract

The superantigen staphylococcal enterotoxin B (SEB) binds to class II MHC expressing cells and subsequently causes selective activation of T cells carrying appropriate T cell receptor (TCR) Vβ chains. Apparently SEB acts as a bifunctional molecule by bridging class II MHC structures with the appropriate TCR-Vβ chains. This assumption predicts that immobilized SEB ought to stimulate purified, class II MHC negative murine T cells. We show here that immobilized SEB lacks the ability to trigger murine CD8 T cells. Responsiveness obtained at a high T cell concentration is due to contaminating class II MHC-positive lymphocytes. Complementation of the culture system with syngeneic irradiated B cells blasts effectively restores responsiveness. The proliferating cells exhibit SEB specific cytotoxicity and a bias for Vβ8 expression. Since no evidence for leakiness of SEB covalently bound to sephadex beads was obtained, the data imply that immobilized SEB in fact binds to the TCR of T cells expressing the appropriate Vβ chains. However, for primary activation additional costimulatory signals are required which can be provided in an unlinked fashion by activated B cells. Resting B cells are activated by immobilized SEB to cells expressing high costimulator activity. As such, the data point out a third function of SEB.