Björn Walse

Crystal structure of a SEA variant in complex with MHC class II reveals the ability of SEA to crosslink MHC molecules.

Although the biological properties of staphylococcal enterotoxin A (SEA) have been well characterized, structural insights into the interaction between SEA and major histocompatibilty complex (MHC) class II have only been obtained by modeling. Here, the crystal structure of the D227A variant of SEA in complex with human MHC class II has been determined by X-ray crystallography. SEA(D227A) exclusively binds with its N-terminal domain to the alpha chain of HLA-DR1. The ability of one SEA molecule to crosslink two MHC molecules was modeled. It shows that this SEA molecule cannot interact with the T cell receptor (TCR) while a second SEA molecule interacts with MHC. Because of its relatively low toxicity, the D227A variant of SEA is used in tumor therapy.

Cutting Edge: Evidence of Direct TCR α-Chain Interaction with Superantigen

Superantigens are known to activate a large number of T cells. The SAg is presented by MHC class II on the APC and its classical feature is that it recognizes the variable region of the β-chain of the TCR. In this article, we report, by direct binding studies, that staphylococcal enterotoxin (SE) H (SEH), a bacterial SAg secreted by Staphylococcus aureus, instead recognizes the variable α-chain (TRAV27) of TCR. Furthermore, we show that different SAgs (e.g., SEH and SEA) can simultaneously bind to one TCR by binding the α-chain and the β-chain, respectively. Theoretical three-dimensional models of the penta complexes are presented. Hence, these findings open up a new dimension of the biology of the staphylococcal enterotoxins.