Streptococcal superantigens

Superantigens (SAgs) are the most powerful T cell mitogens ever discovered. They activate the immune system by binding to the major histocompatibility complex (MHC) class II and T cell receptor molecules. One of the major producers of SAgs is Streptococcus pyogenes, or group A streptococcus (GAS). The recent completion of several GAS genome projects resulted in a sharp rise of novel streptococcal SAgs that were identified by database mining. Orthologue genes of several streptococcal SAgs have also been found in non-GAS, such as Streptococcus equi and Streptococcus disgalactiae. Crystal structure analyses have shown a common protein fold for all streptococcal SAgs analyzed thus far. Furthermore, cocrystal structures of SAgs complexed with MHC class II and T cell receptor Beta-chains, respectively, have provided further insight into the molecular interactions of these toxins with their host cell receptors. This chapter will also discuss the potential involvement of SAgs in severe GAS disease, in particular the highly lethal streptococcal toxic shock syndrome.