Superantigens: Mechanism of T-Cell Stimulation and Role in Immune Responses

Abstract

Superantigens combine with MHC class-II molecules to form the ligands that stimulate T cells via the V beta element of the T-cell receptor. Two groups of superantigens have been described so far: first, endogenous murine products that include the Mls determinants, and second, bacterial products such as the Staphylococcal enterotoxins. Here, we review studies that address the interactions between the foreign superantigens and MHC class-II molecules, the mechanism of T-cell stimulation, and the role that tolerance to self-superantigens plays in shaping the T-cell repertoire. We speculate on the possible evolutionary significance of superantigens.

Identification of the functional region on the superantigen Yersinia pseudotuberculosis‐derived mitogen responsible for induction of lymphocyte proliferation by using synthetic peptides

“…In order to stimulate T-cells, a superantigen has to interact with both the MHC class II molecule and the VI3 domain of TCR. Therefore, two kinds of interface are present on a superantigen molecule, one is for the class II MHC molecule and the other is for the TCR VI3 domain [7,8]. At present, we cannot conclude whether the N-terminal region of the YPM molecule constitutes the interface for the class II MHC molecule, the VI3 domain of TCR, or both.…”

“…The result of these interactions is proliferation of a large number of T-cells with consequent release of cytokines. This ability of superantigens directly accounts for their pathogenic effects and clinical symptoms of the infection [7,8].…”

A method for production of antibodies to human T-cell receptor beta-chain variable regions.

“…Exceptions to this rule have been documented by us and others. These are proteins that stimulate T cells bearing the appropriate V13 element almost independently ofcontributions from other parts of the TCRs borne by the T cells (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Such proteins, called superantigens because they stimulate large numbers ofT cells, are encoded by microorganisms including retroviruses, bacteria, and mycoplasma (22)(23)(24)(25)(26)(27)(28)(29).…”

“…However, much has already been learned from studies of the distribution between animals of just one of the TCR variable elements, V13. Examination of V13 expression in mice has been used to study positive selection, T-cell tolerance, autoimmunity, and the consequences of attack by superantigens (22).…”

“…Experiments of this type have been done in mice by using an ever increasing collection of anti-mouse V13 monoclonal antibodies, raised, usually, against T-cell hybridomas bearing particular V13 elements (22). Similar experiments in humans have been hampered because so far very few anti-human V13…”