Superantigens produced by infectious pathogens: molecular mechanism of action and biological significance

Summary “Superantigens” have in common an extremely potent stimulatory activity for CD4⁺, CD8⁺, and some γδ⁺ T lymphocytes. Superantigens use a unique mechanism: they crosslink variable parts of the T cell receptor with MHC class II molecules on accessory or target cells. The interaction site on the T cell receptor is the variable part of the β-chain (V_β). There are several reasons why these molecules have aroused such tremendous interest in recent years. First, they have provided key information on tolerance mechanisms, both on the deletion of T cells in the thymus and on the induction of peripheral tolerance by anergy and apoptosis. Second, of all polyclonal T cell stimulators they are the ones that most closely mimic the recognition of specific antigen. Finally, they have been recognized as important factors in the pathogenicity of the producing pathogens, inducing shock and immunosuppression. Moreover, it has been postulated that superantigens could be involved in the pathogenesis of certain human diseases.