Superantigens: Just Like Peptides Only Different

The exotoxins produced by Staphylococcus aureus and Streptococcus pyogenes are prototype molecules for the larger family of superantigens (SAGs). This family now includes many structurally unrelated molecules of disparate origins reflecting a wide evolutionary convergence towards the common goal of subverting T cell antigen recognition. SAGs bind simultaneously to MHC class II molecules and TCRs, bringing them together in such a way as to induce profound T cell activation. How SAGs, and in particular the staphylococcal enterotoxins do this, has been the subject of intense interest over the last nine years. It's the subject of an elegant paper from Leder et al. at the Center for Advanced Research at the University of Maryland published in this issue of the Journal of Experimental Medicine (1). This paper examines the thermodynamics of staphylococcal enterotoxin (SE) B and C3 binding to TCR and ultimately raises questions about how similar peptides...