Staphylococcal and Streptococcal Superantigens Trigger B7/CD28 Costimulatory Receptor Engagement to Hyperinduce Inflammatory Cytokines

Discussion Our results show that the ability of diverse staphylococcal and streptococcal superantigens to bind directly to CD28 (4) and to B7-2 (5) is matched by a general ability to promote B7-2/CD28 engagement underlying formation of the primary costimulatory axis mandatory for T-cell activation. Indeed, these superantigens promote not only the between B7-2 and CD28 which occurs with low affinity but also the interaction between B7-1 and CD28 which occurs with far higher affinity. This property of the superantigen toxins can explain not only why they elicit an inflammatory cytokine storm resulting in lethality and toxic shock but also why homodimer interface mimetic peptides derived from CD28 or from B7-2 attenuate their ability to induce inflammatory cytokines (4, 5), illustrated here also for SMEZ. Diverse superantigens differ significantly in terms of their mode of interaction with the α- and β-chains of the MHC-II molecule: SEB, TSST-1 and SPEA bind only to the α-chain and SMEZ binds exclusively to the β-chain, whereas SEA engages both α- and β-chains (28, 29). Despite these pronounced differences in binding to MHC-II molecule, and a 40-fold difference in terms of toxicity between SEB and SMEZ (30), each of the superantigens we examined showed a very similar ability to promote B7-2/CD28 engagement. Moreover, this property extends to the ability of staphylococcal as well as streptococcal superantigens to enhance B7-1/CD28 ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research