ACTIVATION OF MURINE T-CELLS BY BACTERIAL SUPERANTIGENS REQUIRES B7-MEDIATED COSTIMULATION

Staphylococcus enterotoxins bind class II MHC molecules on antigen-pre senting cells (APC) and stimulate T cells expressing appropriate V bet a gene products. Although the role of non-TcR-associated costimulatory receptors during antigen-specific T cell stimulation has been clearly established, the involvement of costimulatory activity in T cell acti vation by superantigens (SAgs) has been the matter of controversy. The aim of this study was to evaluate the role of the costimulatory-recep tor ligand molecules CD28/B7 on bacterial SAg-mediated activation of n aive murine T cells. We demonstrate in this report that a combination of monoclonal antibodies to murine B7.1 and B7.2 molecules inhibits th e in vitro response of naive T cells to SAgs SEA, SEE, and TSST-1. The inhibition of T cell responses required simultaneous blocking of B7.1 and B7.2, suggesting that either B7.1 or B7.2 is sufficient to provid e costimulatory signals to naive T cells in response to bacterial exot oxins. Inhibition of T cell activation by antibodies to B7-related mol ecules can be overcome by antibodies to CD28, a finding in agreement w ith the hypothesis that CD28-mediated signals participate in T cell ac tivation by bacterial SAgs. These observations suggest that, as demons trated for conventional antigen, T cell activation by SAgs requires th e coordinated participation of TcR- and CD28-derived signals. (C) 1995 Academic Press, Inc.