Superantigens: structure and relevance to human disease.

Superantigens are a class of immunostimulatory molecules produced by bacteria and viruses. Their potent immune effects are due to their unique ability to bind to the major histocompatibility complex (MHC) outside the antigen-binding cleft and to stimulate T cells in a T-cell receptor (TCR) Vbeta-specific manner. Structural studies have revealed the binding sites involved in the MHC/superantigen/TCR complex. The bacterial superantigens are responsible for a number of syndromes, including food poisoning and toxic shock syndrome, but their effects may be not only acute but also chronic and complex. Recent evidence suggests that superantigens may be relevant to the pathogenesis of autoimmune and immunodeficiency disorders. To illustrate the detrimental effects of superantigens on disease outcome, evidence demonstrating the modulation of experimental allergic encephalomyelitis, an animal model for multiple sclerosis, by superantigen, as well as the potential role of superantigens in HIV pathogenesis of AIDS, will be presented. The information presented may provide valuable insight into the role of superantigens in autoimmunity and HIV infection.