The TCR Vbeta signature of bacterial superantigens spreads with stimulus strength

Llewelyn, Martin, Sriskandan, Shiranee, Terrazzini, Nadia, Cohen, Jonathan and Altmann, Daniel M (2006) The TCR Vbeta signature of bacterial superantigens spreads with stimulus strength. International Immunology, 18 (10). pp. 1433-1441. ISSN 0953-8178

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Superantigens (Sags) induce large-scale stimulation of T lymphocytes by a mechanism distinct from conventional antigen presentation, involving direct MHC binding and stimulation of TCR families based on Vbeta gene usage. The specific Vbeta targets of a given Sag have, since the earliest studies in murine models, been considered a hallmark of that toxin. Bacterial Sags are implicated in the aetiology of a wide range of human diseases, although their role has been most clearly defined in toxic shock syndrome. While Sags have been defined by the Vbeta-specific changes in T cell repertoire they induce, human studies of in vitro stimulation or analysis of cells from infected patients have produced inconsistent findings. Here we have evaluated the contribution of HLA allelic polymorphisms and strength of stimulus to this response. We show that there are differences in binding and presentation of the staphylococcal Sag, staphylococcal enterotoxin A (SEA), by different HLA-DR alleles. We also show that the TCR Vbeta response, previously thought to be a fixed property defining a given Sag, varies with stimulus strength such that a broader repertoire of response is seen at higher concentrations or following presentation by high-binding class II types. Responses of human Vbeta8 and Vbeta1 to SEA, Vbeta5 to SEB and of Vbeta12 and Vbeta13 to streptococcal pyrogenic exotoxin A are absolutely dependent on stimulus strength. These findings have important implications for heterogeneity in the response to Sags and the consequent differences in susceptibility to severe toxic shock.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Global Health and Infection
Depositing User: Sandy Gray
Date Deposited: 12 Sep 2016 15:49
Last Modified: 21 Sep 2017 14:17
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