International Immunology Advance Access originally published online on August 7, 2006
International Immunology 2006 18(10):1433-1441; doi:10.1093/intimm/dxl076
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The TCR Vß signature of bacterial superantigens spreads with stimulus strength
1 Department of Infectious Diseases, Faculty of Medicine, Imperial College London W12 0NN, UK
2 Division of Medicine, Brighton and Sussex Medical School, Medical Research Building, University of Sussex, Falmer BN1 9PS, UK
Correspondence to: M. Llewelyn; E-mail: m.j.llewelyn{at}bsms.ac.uk
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 Vß gene usage. The specific Vß 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 Vß-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 Vß 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 Vß8 and Vß1 to SEA, Vß5 to SEB and of Vß12 and Vß13 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.
Keywords: bacterial, human, superantigens, T cells, TCRs
Transmitting editor: M. Feldman
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