Nasopharyngeal infection byStreptococcus pyogenesrequires superantigen-responsive Vβ-specific T cells

Significance Superantigen toxins were defined over 25 years ago for their ability to activate T cells in a T-cell receptor β-chain variable domain-dependent manner. This “Vβ-specific” T-cell activation is the hallmark feature of the superantigen, and although these toxins can mediate dangerous human disease such as toxic shock syndrome, mechanisms that explain why bacteria produce superantigens have remained enigmatic. Herein, we provide evidence that Streptococcus pyogenes utilizes superantigens to target functional, Vβ-specific T cells to promote a state of colonization providing a mechanism that helps explain why bacteria produce toxins that specifically activate T cells of the adaptive immune system. This work also implicates the superantigen exotoxins as potential vaccine candidates against this globally important, human-specific pathogen.