Structural basis for the recognition of superantigen streptococcal pyrogenic exotoxin A (SpeA1) by MHC class II molecules and T-cell receptors

Streptococcal pyrogenic exotoxin A (SpeA) is a superantigen produced by Str eptococcus pyogenes and is associated with severe infections characterized by rash, hypotension, multiorgan failure and a high mortality rate. In this study, an allelic form of this toxin, SpeAl, was crystallized with four mo lecules in the crystallographic asymmetric unit and its crystal structure w as determined at 2.6 Angstrom resolution. The crystallographic R-factor was 19.4% (33497 reflections) for 7031 protein atoms and 88 water molecules. T he overall structure of SpeAl is considerably similar to that of other prot otype microbial superantigens, either of staphylococcal or streptococcal or igin, but has greatest similarity to staphylococcal enterotoxin C (SEC), Ba sed on structural and mutagenesis data, we have mapped several important re sidues on the toxin molecule, which are involved in the recognition of majo r histocompatibility complex (MHC) class LI molecules and T-cell receptors, Also, the toxin appears to possess a potential zinc-binding site which may have implications in binding to particular MHC class II molecules. Finally , we propose models for SpeA1-MHC class II and SpeA1-T-cell receptor associ ation and the relevance of this phenomenon to the superantigenic action of this toxin is considered.