Author:
Kunkl Martina,Amormino Carola,Spallotta Francesco,Caristi Silvana,Fiorillo Maria Teresa,Paiardini Alessandro,Kaempfer Raymond,Tuosto Loretta
Abstract
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.
Funder
Associazione Italiana Sclerosi Multipla
Associazione Italiana per la Ricerca sul Cancro
Subject
Immunology,Immunology and Allergy