STRUCTURAL DICHOTOMY OF STAPHYLOCOCCAL-ENTEROTOXIN-C SUPERANTIGENS LEADING TO MHC CLASS-II-INDEPENDENT ACTIVATION OF T-LYMPHOCYTES

We have recently characterized an MHC class II deficient human cell li ne, SW480, that supports the proliferation of purified human T cells i n the presence of the staphylococcal enterotoxin and superantigen SEC1 , but not the closely related isotypes SEC2 or SEC3. We now investigat e the structural basis of this dichotomy and explore possible mechanis ms that may account for it. Differences in activity between SEC1 and S EC2 were not attributable to differences in biochemical modification, to differences in vp specificity, or to the potential to induce anergy , SEC2 inhibited SEC1-mediated T cell activation in the presence of SW 480 cells, suggesting that SEC2 could compete with SEC1 for binding to the TCR but was unable to productively signal through the TCR. Utiliz ing a panel of hybrid enterotoxins we identified specific amino acids near the NH2-terminus of SEC1 that abrogated MHC class II-independent T cell activation, yet did not alter potency in the presence of class II+ APC, These residues mapped to the putative TCR binding domain of S EC1, and suggest that subtle differences in TCR binding affinity or th e topology of the SEC1-TCR interaction can compensate for the lack of MHC class II and hence promote T cell proliferation.