REACTIVITY OF HUMAN GAMMA-DELTA T-CELLS TO STAPHYLOCOCCAL ENTEROTOXINS - A RESTRICTED REACTION PATTERN MEDIATED BY 2 DISTINCT RECOGNITION PATHWAYS

Staphylococcal enterotoxins (SEs) are known superantigens for T cells expressing the alphabeta 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 Vbeta-gene products. The reactivity of gammadelta 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 gammadelta T-cell clones against target cells coated with the enterotoxins SEA, SEB, SEC 1, SEC2, SEC3, SED, SEE or TSST. Three reaction patterns were observed with the gammadelta 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, gammadelta 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 gammadelta T cells to SEs is mediated by two distinct pathways: an antibody-independent and an antibody-dependent pathway. The antibody-independent reactivity of gammadelta T cells was directed to either SEA or SEE, whereas antibody-dependent reactivity was found only towards SEA. The capacity of gammadelta 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.