4.8 Article

Bivalent binding of staphylococcal superantigens to the TCR and CD28 triggers inflammatory signals independently of antigen presenting cells

Journal

FRONTIERS IN IMMUNOLOGY
Volume 14, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2023.1170821

Keywords

staphylococcal superantigens; T cells; TCR (T cell receptor); CD28; inflammation

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Staphylococcus aureus superantigens (SAgs) like staphylococcal enterotoxin A (SEA) and B (SEB) can cause toxic shock and sepsis by stimulating T cells to produce excessive inflammatory cytokines. Using an AI-based algorithm, we have discovered a new mechanism of action for SAgs, showing that SEA and SEB can bind to TCR and CD28 independently of MHC class II- and B7-expressing antigen presenting cells, leading to inflammatory signal activation and massive cytokine secretion.
Staphylococcus aureus superantigens (SAgs) such as staphylococcal enterotoxin A (SEA) and B (SEB) are potent toxins stimulating T cells to produce high levels of inflammatory cytokines, thus causing toxic shock and sepsis. Here we used a recently released artificial intelligence-based algorithm to better elucidate the interaction between staphylococcal SAgs and their ligands on T cells, the TCR and CD28. The obtained computational models together with functional data show that SEB and SEA are able to bind to the TCR and CD28 stimulating T cells to activate inflammatory signals independently of MHC class II- and B7-expressing antigen presenting cells. These data reveal a novel mode of action of staphylococcal SAgs. By binding to the TCR and CD28 in a bivalent way, staphylococcal SAgs trigger both the early and late signalling events, which lead to massive inflammatory cytokine secretion.

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