T Cell Activation by Superantigens—Dependence on MHC Class II Molecules

Abstract

The capacity of certain bacterial exoproducts to act as T cell mitogens has long been recognized (Peary et al. 1970). Similar to other, polyclonal activators, they were found to require the participation of accessory cells (AC). It was later shown that the function of a cell type as AC correlated with its expression of MHC class II (Carlsson et al. 1988; Fleischer and Schrezenmeier 1988). The number of microbial exoproducts shown to act as T cell mitogens in this way has gradually increased and these molecules have been called “superantigens” (SAs) in view of their capacity to activate a large proportion of all T lymphocytes in various species (Marrack and Kappler 1990). The activation is induced by selective interaction with all T cells expressing certain V-β and V-γ chains of the T cell receptor (TCR) regardless of their epitope specificity. Besides other microbial molecules such as the Mycoplasma arthritidis protein MAM (Cole et al. 1981), this group of SAs also includes certain self molecules, the murine Mls antigens (Janeway 1990). There are strong indications that the Mls antigens are encoded by retroviral genes (Marrack et al. 1991; Frankel et al. 1991; Woodland et al. 1991; Dyson et al. 1991). A dependence on class II-expressing AC has been demonstrated for all SAs studied, although at least for some SAs it can be replaced by a combination of other accessory signals. Besides their TCR binding and massive T cell activating capacity, this usage of MHC class II molecules is the most prominent common feature of SAs. With few exceptions this binding to MHC class II is a prerequisite for the T cell activating effects of SAs and is therefore of prime importance in their function.