Abstract
SEVERAL exoproteins from the bacterium Staphylococcus aureus are highly potent polyclonal activators of T cells in the presence of cells bearing class II antigens of the major histocompatibility complex (MHC)1–3. These toxins, including the toxic shock syndrome toxin (TSST-1), act at nanomolar concentrations, bind directly to class II molecules, and do not require the processing typical of nominal antigen3–7. Each toxin is capable of stimulating a subpopulation of peripheral T lymphocytes bearing particular Vβ sequences as part of their αβ T-cell receptors8,9. It is not known how these so-called 'superantigens' bind to class II and how this binding stimulates T cells. In this study, the different affinities of TSST-1 for human class II molecules DR and DP were exploited to define the region of a class II molecule necessary for high-affinity binding. Using chimaeric α- and β-chains of DR and DP expressed at the surface of transfected murine fibroblasts and a binding assay with TSST-1, it was shown that the α1 domain of DR is essential for high-affinity binding, and further that TSST-1 binding did not prevent subsequent binding of a DR-restricted antigenic peptide. This is compatible with a model of superantigen making external contacts with both class II and T cell receptor, and suggests that the Vβ portion of the T-cell receptor interacts with the nonpolymorphic α-chain of DR.
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Karp, D., Teletski, C., Scholl, P. et al. The α1 domain of the HLA-DR molecule is essential for high-affinity binding of the toxic shock syndrome toxin-1. Nature 346, 474–476 (1990). https://doi.org/10.1038/346474a0
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DOI: https://doi.org/10.1038/346474a0
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