Superantigens.

"Superantigens" is the term for a group of molecules that have in common an extremely potent stimulatory activity for T lymphocytes of several species. They stimulate CD4+, CD8+ and gamma delta + T cells by a unique mechanism: they cross-link variable parts of the T-cell receptor (TCR) with MHC class II molecules on accessory or target cells. The interaction site on the class II molecule and on the TCR is different from the peptide binding site; on the TCR it is the variable part of the beta chain (V beta). The prototype superantigen is the staphylococcal enterotoxin B (SEB), member of a family of genetically related proteins produced by Staphylococcus aureus and Streptococcus pyogenes. These are soluble exotoxins of approximately 27 kd molecular mass. It is intriguing that this molecular mechanism of T-cell stimulation has been independently produced at least three times in evolution. Other pathogens producing superantigens are retroviruses (the Mouse Mammary Tumor Viruses) and a mycoplasma (Mycoplasma arthritidis). Many additional candidate superantigens have been proposed, but in most cases unequivocal evidence for superantigen activity is still missing. 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. Whilst there is evidence that superantigens could be involved in the pathogenesis of certain human diseases, in most cases this is still very preliminary and indirect.