An antigen produced by bacteria or viruses that cause non-specific activation of T-lymphocytes. Superantigens form crosslinks between either two major histocompatibility class (MHC) II molecules, which increases both cytokine expression and costimulatory receptor expression in antigen presenting cells, or one MHC class II molecule and the variable region of the T-cell receptor beta chain, which results in increased proliferation of and cytokine expression by T-lymphocytes. This non-specific release of cytokines and upregulation of immune cell activation can lead to rashes, fever, vomiting, anergy, and damage to tissues and organs. These symptoms can progress to autoimmunity, multi-organ failure, coma and death.

Class of bacterial and viral proteins which stimulate a large proportion of T lymphocytes based on the expression of specific T cell antigen receptor Vbeta elements and thus do not require antigen processing by MHC class II molecules.

Microbial antigens that have in common an extremely potent activating effect on T-cells that bear a specific variable region. Superantigens cross-link the variable region with class II MHC proteins regardless of the peptide binding in the T-cell receptor's pocket. The result is a transient expansion and subsequent death and anergy of the T-cells with the appropriate variable regions.