MICROBIAL SUPERANTIGENS STIMULATE T-CELLS BY THE SUPERANTIGEN BRIDGE AND INDEPENDENTLY BY A CYTOKINE PATHWAY

Superantigens cross-link the MHC II molecule on accessory cells with t he V beta region of the T cell receptor (TCR), In this study, we compa red the capacity of established superantigens for inducing cytokine re lease. The experimental protocol was generated to answer the question whether all superantigen effects are transmitted by the MHC/TCR cross- linkage and induce mainly a T cell response, We found that TSST-1, ExF TA, and SEC3 differed from all other superantigens tested because they stimulated a stronger monokine release, T cell proliferation after ch allenge with these superantigens was mainly mediated by a cytokine pat hway and not by the cross-linkage of MHC and TCR, For the other supera ntigens, we were able to demonstrate that major immunomodulatory effec t is mediated by the superantigen bridge, With the exception of these three superantigens, the proliferative response of superantigens corre lated with their V beta specificity, Interleukin-1 (IL-1) and IL-6 wer e induced in monocytes by all superantigens, whereas tumor necrosis fa ctor-alpha (TNF-alpha) was induced in T cells and by some superantigen s, also in monocytes, IL-2 was always induced by the superantigen brid ge, whereas interferon-gamma (IFN-gamma) was also induced indirectly b y monokines, Collectively, our results indicate that not all superanti gens are suitable for investigating superantigen-specific effects, as they show indirect (mitogenic) side effects, Observations for an indiv idual superantigen are, therefore, not transferable to all other super antigens.