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Reactivity of Human γδ T Cells to Staphylococcal Enterotoxins: a Restricted Reaction Pattern mediated by Two Distinct Recognition Pathways

Staphylococcal enterotoxins (SEs) are known superantigens for T cells expressing the αβ T‐cell receptor (TCR). They bind to MHC class II molecules on antigen‐presenting cells and can subsequently trigger T‐cell responses by binding to Vβ‐gene products. The reactivity of γδ T cells with enterotoxins is less well defined although both proliferative and cytotoxic responses have been described. In the present study we have tested the cytotoxic reactivity of a panel of 41 γδ T‐cell clones against target cells coated with the enterotoxins SEA, SEB, SEC1, SEC2, SEC3, SED, SEE or TSST. Three reaction patterns were observed with the γδ T‐cell clones: (1) clones that specifically lysed SEA‐coated target cells only; (2) clones that specifically lysed SEE‐coated target cells only, and (3) clones that specifically lysed SEA‐coated target cells only in the presence of certain human sera. The presence of SEA‐specific antibodies in such human sera could be demonstrated. Moreover, γδ T‐ cell clones of this third category expressed the IgG FcRIII (CD16) which indicates that these clones are capable of mediating antibody‐dependent cellular cytotoxicity towards SEA‐coated target cells. Thus, the cytotoxic response of γδ T cells to SEs is mediated by two distinct pathways: an antibody‐independent and an antibody‐dependent pathway. The antibody‐independent reactivity of γδ T cells was directed to either SEA or SEE, whereas antibody‐dependent reactivity was found only towards SEA. The capacity of γδ T‐cell clones to respond to stimulation with SEs, combined with their high cytolytic capacity in vitro, suggests that these cells can be involved in SE‐directed immune responses and efficiently kill SE‐coated target cells in vivo.