A superantigen is an antigen bound by antibodies found in the preimmune repertoire without the requirement of adaptive maturation of antibody variable domains.

A bacterial toxin that is capable of stimulating multiple T lymphocytes, leading to the release of relatively large quantities of cytokines is a superantigen. Superantigens bind simultaneously to the VB domain of the T cell receptor and  molecule, activating all T cells bearing a particular VB domain. Because of this binding ability, superantigens can activate large numbers of T cells irrespective of their antigenic specificity. Although less than 0.01% of T cells respond to a given conventional antigen, up to 25% can respond to a given superantigen. The large number of T cells activated results in excessive production of .

Encounter with antigens generally stimulates B cell proliferation. SAg binding to the B cell receptor, on the other hand, is thought to induce cellular apoptosis (Paul, US 11988761). 

Both exogenous and endogenous superantigens have been identified. Crosslinkage of a T cell receptor and class II MHC molecule by either type of superantigen produces an activating signal that induces T-cell activation and proliferation.

Exogenous Superantigens

Exogenous superantigens are soluble proteins secreted by bacteria. Each of these exogenous superantigens binds particular V beta sequences in T cell receptors and crosslinks the TCR to a Class II MHC molecule.Some of these toxins include:

• staphylococcal enterotoxins

• toxic shock syndrome toxin which induces high levels of TNF and IL-1 which can induce systemic reactions that include fever, widespread blood clotting and shock.

• exfoliative dermatitis toxin

Bacterial Superantigens:

Bacterial sueprantigens (Sags) are a well described family of 40 secrected protein toxins produced by Staphylococcus aureus and Streptococcus pyogenes with orthologues exisiting in group C Streptococcus equi and group G Streptococcus disgalactiae. Two quite unrelated Sags are also produced by Mycoplasma arthriditis mitigen (MAM) and Yersina pseudotuberculosis mitogen (YPM). MAM is unrelated by amino acid sequence homology to members of the staphylococcal/streptococcal Sag family. Systemic intoxication by a Sag can lead to the life-threatening condition toxic shock syndrome (TSS) caused by a sudden cytokine storm when large numbers of T cells are sitmulated by the Sag cross-linking MHC class II antigens and T-cell receptors (TCR). Scarlet fever is caused by pharyngeal infection of group A streptococcus (GAS) and was a common childhood illness world wide during the first half of the 20th centure. Sags are thus virulence factors that target the adaptive response through the immunological synapse. They are noted for their extreme potenecy with some members stimulating human T cells in vitro at 1 gemtogram/ml, a feature that highlights the ezquisite sensitivity of T cell recognition of MHC bound antigen. Fraser “The bacterial superantigen and superantigen-like protein” Immunological Reviews, 2008). 

Endogenous Superantigens

Endogenous superantigens are cell membrane proteins encoded by certain viruses that infect mammalian cells.

Examples of of endogenous superantigens are the HIV coat protein gp120, HIV Tat and Staphylococcal Protein A. gp120 contains an antigenic site recognized by Abs present in the preimmune repertoire of humans free of HIV infection. This qualified gp120 for designation as a B cell Sag because it is an antigen bound by Abs without the requirement of adaptive sequence diversification of Ab V domains. Synthetic peptide studies suggest that the gp120 SAg site is a conformational epitope composed of peptide determinants 231-260, 331-360 and 421-440 (Paul, US 11988761).