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Activation of the TCR Complex by Peptide-MHC and Superantigens

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T Lymphocytes as Tools in Diagnostics and Immunotoxicology

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

Abstract

Drug hypersensitivity reactions are immune mediated, with T lymphocytes being stimulated by the drugs via their T-cell antigen receptor (TCR). In the nonpathogenic state, the TCR is activated by foreign peptides presented by major histocompatibility complex molecules (pMHC). Foreign pMHC binds with sufficient affinity to TCRαβ and thereby elicits phosphorylation of the cytoplasmic tails of the TCRαβ-associated CD3 subunits. The process is called TCR triggering. In this review, we discuss the current models of TCR triggering and which drug properties are crucial for TCR stimulation. The underlying molecular mechanisms mostly include pMHC-induced exposure of the CD3 cytoplasmic tails or alterations of the kinase-phosphatase equilibrium in the vicinity of CD3. In this review, we also discuss triggering of the TCR by small chemical compounds in context of these general mechanisms.

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Acknowledgments

This work was funded by the EU through grant FP7/2007–2013 (SYBILLA) and the Deutsche-Forschungsgemeinschaft (DFG) by the Excellence Initiative of the German Research Foundation (EXC294, the Center for Biological Signalling Studies, BIOSS, and GSC-4, Spemann Graduate School), SFB620 B6 and SCHA 976/2-1.

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Authors and Affiliations

  1. Department of Molecular Immunology, Institute for Biology III, Faculty of Biology, BIOSS Center for Biological Signalling Studies, Centre for Chronic Immunodeficiency CCI, University of Freiburg and Max Planck-Institute of Immunobiology and Epigenetics, Freiburg, Germany

    Christine Louis-Dit-Sully, Britta Blumenthal, Marlena Duchniewicz, Esmeralda Beck-García, Markus Mukenhirn, Susana Minguet & Wolfgang W. A. Schamel

  2. Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg, Germany

    Katharina Beck-Garcia & Gina J. Fiala

  3. International Max Planck Research School for Molecular and Cellular biology (IMPRS-MCB), Max Planck-Institute of Immunobiology and Epigenetics, Freiburg, Germany

    Esmeralda Beck-García

Authors
  1. Christine Louis-Dit-Sully
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  2. Britta Blumenthal
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  3. Marlena Duchniewicz
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  4. Katharina Beck-Garcia
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  5. Gina J. Fiala
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  6. Esmeralda Beck-García
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  7. Markus Mukenhirn
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  8. Susana Minguet
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  9. Wolfgang W. A. Schamel
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Corresponding author

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. et al. (2014). Activation of the TCR Complex by Peptide-MHC and Superantigens. 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_2

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