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Novel insights into the immune response to bacterial T cell superantigens

Nature Reviews Immunology (2024)Cite this article

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Abstract

Bacterial T cell superantigens (SAgs) are a family of microbial exotoxins that function to activate large numbers of T cells simultaneously. SAgs activate T cells by direct binding and crosslinking of the lateral regions of MHC class II molecules on antigen-presenting cells with T cell receptors (TCRs) on T cells; these interactions alter the normal TCR–peptide–MHC class II architecture to activate T cells in a manner that is independent of the antigen specificity of the TCR. SAgs have well-recognized, central roles in human diseases such as toxic shock syndrome and scarlet fever through their quantitative effects on the T cell response; in addition, numerous other consequences of SAg-driven T cell activation are now being recognized, including direct roles in the pathogenesis of endocarditis, bloodstream infections, skin disease and pharyngitis. In this Review, we summarize the expanding family of bacterial SAgs and how these toxins can engage highly diverse adaptive immune receptors. We highlight recent findings regarding how SAg-driven manipulation of the adaptive immune response may operate in multiple human diseases, as well as contributing to the biology and life cycle of SAg-producing bacterial pathogens.

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Fig. 1: Phylogenetic relationships and representative structures of bacterial superantigens.
Fig. 2: Structural overview of T cell activation by bacterial superantigens.
Fig. 3: Forced manipulation of T cell signalling can have broad effects on multiple T cell responses.
Fig. 4: Phenotypic responses to streptococcal and staphylococcal superantigens.
Fig. 5: The contributions of staphylococcal superantigens to atopic dermatitis, chronic rhinosinusitis and bacteraemia.

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Acknowledgements

This work was supported by the Canadian Institutes of Health Research (project grant PJT-166050 to S.W.T. and J.K.M., and project grant PJT-461623 to J.K.M.). A.R. acknowledges support from an R.G.E. Murray Graduate Scholarship.

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    Stephen W. Tuffs, Karine Dufresne, Aanchal Rishi, Nicholas R. Walton & John K. McCormick

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Tuffs, S.W., Dufresne, K., Rishi, A. et al. Novel insights into the immune response to bacterial T cell superantigens. Nat Rev Immunol (2024). https://doi.org/10.1038/s41577-023-00979-2

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