So many ways of getting in the way: diversity in the molecular architecture of superantigen-dependent T-cell signaling complexes

Superantigens (SAGs) elicit massive T-cell proliferation through simultaneous interaction with MHC and TCR molecules. SAGs have been implicated in toxic shock syndrome and food poisoning, and they may also play a pathogenic role in autoimmune diseases. The best-characterized group of SAGs are the pyrogenic bacterial SAGs, which utilize a high degree of genetic variation on a common structural scaffold to achieve a wide range of MHC-binding and T-cell-stimulating effects while assisting pathogen evasion of the adaptive immune response. Several new structures of SAG–MHC and SAG–TCR complexes have significantly increased understanding of the molecular bases for high-affinity peptide/MHC binding by SAGs and for TCR Vβ domain specificity of SAGs. Using the currently available SAG–MHC and SAG–TCR complex structures, models of various trimolecular MHC–SAG–TCR complexes may be constructed that reveal wide diversity in the architecture of SAG-dependent T-cell signaling complexes, which nevertheless may result in similar signaling outcomes.