Abstract
Small chemical compounds and certain metal ions can activate T cells, resulting in drug hypersensitivity reactions that are a main problem in pharmacology. Mostly, the drugs generate new antigenic epitopes on peptide-major histocompatibility complex (MHC) molecules that are recognized by the T-cell antigen receptor (TCR). In this review we discuss the molecular mechanisms of how the drugs alter self-peptide-MHC, so that neo-antigens are produced. This includes (1) haptens covalently bound to peptides presented by MHC, (2) metal ions and drugs that non-covalently bridge self-pMHC to the TCR, and (3) drugs that allow self-peptides to be presented by MHCs that otherwise are not presented. We also briefly discuss how a second signal—next to the TCR—that naïve T cells require to become activated is generated in the drug hypersensitivity reactions.
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Acknowledgements
We thank Stefan Martin for discussions on this topic. This work was funded by the EU through grant FP7/2007–2013 (SYBILLA) and the Deutsche-Forschungsgemeinschaft (DFG) through EXC294 (the Center for Biological Signalling Studies, BIOSS).
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Louis-Dit-Sully, C., Schamel, W.W.A. (2014). Activation of the TCR Complex by Small Chemical Compounds. In: Martin, S. (eds) T Lymphocytes as Tools in Diagnostics and Immunotoxicology. Experientia Supplementum, vol 104. Springer, Basel. https://doi.org/10.1007/978-3-0348-0726-5_3
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