STAPHYLOCOCCAL-ENTEROTOXIN-A AND TOXIC-SHOCK-SYNDROME TOXIN COMPETE WITH CD4 FOR HUMAN MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II BINDING

We have examined the role of the CD4 molecule in primary T-lymphocyte responses to the staphylococcal enterotoxins SEA, SEE, SEC1, and the toxic shock syndrome toxin TSST-1. Proliferating cells were predominantly CD4(+); however, the responses to SEA and TSST-1 were most sensitive to inhibition by the anti-CD4 antibody Leu-3a. T-lymphocyte responses to the bacterial superantigens were inhibited by site-directed mutations of residues in the DR beta membrane-proximal domain (DR beta(2)) that are also known to be important for interactions with CD4. SEA and TSST-1 binding to DR was reduced by the DR beta(2) mutations and by competition with soluble recombinant CD4. We propose that bacterial superantigens sequentially, or simultaneously with CD4, stabilize complexes of T-cell antigen receptors and major histocompatibility complex class II molecules. The superantigen qualities of these toxins may be due, in part, to a molecular mimicry of CD4 and other adhesion molecules.