INTERCELLULAR-ADHESION MOLECULE-1 AND LEUKOCYTE FUNCTION-ASSOCIATED ANTIGEN-3 PROVIDE COSTIMULATION FOR SUPERANTIGEN-INDUCED T-LYMPHOCYTE PROLIFERATION IN THE ABSENCE OF A SPECIFIC PRESENTING MOLECULE

Bacterial superantigens can bind TCR in tine absence of MHC class II m olecules and activate T lymphocytes when cocultured with certain class Il-deficient accessory cells. It has not been determined, however, wh ether these accessory cells provide direct costimulation to the T cell or serve to present superantigens via a nonconventional ligand. We ha ve identified a human adenocarcinoma cell line, SW480, that assists in the activation of human T cells by the staphylococcal enterotoxins B (SEE), Ct (SEC1), and D (SED), but not SEA, SEC2, SEC3, or SEE. SW480 cells did not express class II molecules, and anti-class II mAbs did n ot inhibit T cell proliferation, supporting the hypothesis that class II is not absolutely required for enterotoxin-mediated T cell activati on. The TCR VP profile of T cells stimulated by SEE plus SW480 cells w as similar to that of T cells stimulated by SEE plus class II+ APC, in dicating that TCR-SEB interactions were preserved in the absence of cl ass II molecules. Binding studies failed to detect specific associatio n of SEE with SW480 cells, suggesting that SW480 cells do not express receptors for enterotoxin. SEE coupled to beads, however, stimulated T cell proliferation, but only in the presence of SW480 cells. SW480 ce lls express both ICAM-1 and LFA-3 molecules, and the addition of Abs t o these receptors inhibited T cell proliferation. These findings suppo rt a model in which certain enterotoxins engage the TCR independent of MHC class II or other specific presenting molecules and induce T cell proliferation with signals provided by nonconventional accessory cell s.