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T Lymphocytes as Tools in Diagnostics and Immunotoxicology pp 25–39Cite as

Activation of the TCR Complex by Small Chemical Compounds

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Part of the book series: Experientia Supplementum ((EXS,volume 104))

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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Authors and Affiliations

  1. Faculty of Biology, Department of Molecular Immunology, Institute of Biology III, University of Freiburg, Freiburg, Germany

    Christine Louis-Dit-Sully

  2. BIOSS Centre for Biological Signaling Studies, University of Freiburg, Freiburg, Germany

    Christine Louis-Dit-Sully & Wolfgang W. A. Schamel

  3. Centre for Chronic Immunodeficiency CCI, University Clinics Freiburg and Medical Faculty, University of Freiburg, Freiburg, Germany

    Wolfgang W. A. Schamel

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  1. Christine Louis-Dit-Sully
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  2. Wolfgang W. A. Schamel
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Correspondence to Wolfgang W. A. Schamel .

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Editors and Affiliations

  1. Department of Dermatology and Venereology, University Medical Center Freiburg, Freiburg, Germany

    Stefan F. Martin

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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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