Structural basis of supantigen action inferred from crystal structure of toxic-shock syndrome toxin-1

SUPERANTIGENS stimulate T cells bearing particular T-cell receptor Vβ sequences^1,2, so they are extremely potent polyclonal T-cell mitogens. T-cell activation is preceded by binding of superantigens to class II major histocompatibility complex (MHC) molecules³. To further the structural characterization of these interactions, the crystal structure of a toxin associated with toxic-shock syndrome, TSST-1, which is a microbial supantigen, has been determined at 2.5 Å resolution. The N- and C-terminal domains of the structure both contain regions involved in MHC class II association; the C-terminal domain is also implicated in binding the T-cell receptor. Despite low sequence conservation, the TSST-1 topology is similar to the structure reported for the supantigen staphylococcal enterotoxin B ⁴. But TSST 1 lacks several of the structural features highlighted as central to supantigen activity in the staphylococcal enterotoxin B and we therefore reappraise the structural basis of supantigen action.