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Structural understanding of T cell receptor triggering

Cellular & Molecular Immunology volume 17, pages 193–202 (2020)Cite this article

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Abstract

The T cell receptor (TCR) is one of the most complicated receptors in mammalian cells, and its triggering mechanism remains mysterious. As an octamer complex, TCR comprises an antigen-binding subunit (TCRαβ) and three CD3 signaling subunits (CD3ζζ, CD3δε, and CD3γε). Engagement of TCRαβ with an antigen peptide presented on the MHC leads to tyrosine phosphorylation of the immunoreceptor tyrosine-based activation motif (ITAM) in CD3 cytoplasmic domains (CDs), thus translating extracellular binding kinetics to intracellular signaling events. Whether conformational change plays an important role in the transmembrane signal transduction of TCR is under debate. Attracted by the complexity and functional importance of TCR, many groups have been studying TCR structure and triggering for decades using diverse biochemical and biophysical tools. Here, we synthesize these structural studies and discuss the relevance of the conformational change model in TCR triggering.

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Acknowledgements

We thank Wei Wu and Chengsong Yan for thoughtful discussions. C.X. is funded by CAS grants (Strategic Priority Research Program XDB29000000, Facility-based Open Research Program QYZDB-SSW-SMC048, Fountain-Valley Life Sciences Fund of University of Chinese Academy of Sciences Education Foundation), NSFC grant (31861133009, 31621003), MOST Grant (2018YFA0800700) and the Ten Thousand Talent Program “Leading Talent” of China. H.L. is funded by an NSFC grant (31670751).

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  1. These authors contributed equally: Xinyi Xu, Hua Li

Authors and Affiliations

  1. State Key Laboratory of Molecular Biology, Shanghai Science Research Center, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences; University of Chinese Academy of Sciences, 320 Yueyang Road, 200031, Shanghai, China

    Xinyi Xu, Hua Li & Chenqi Xu

  2. School of Life Science and Technology, ShanghaiTech University, 100 Haike Road, 201210, Shanghai, China

    Chenqi Xu

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  1. Xinyi Xu
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  2. Hua Li
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C.X. designed the framework. X.X. wrote the manuscript. H.L. and C.X. revised it. H.L. and X.X. made the figures.

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Correspondence to Chenqi Xu.

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Xu, X., Li, H. & Xu, C. Structural understanding of T cell receptor triggering. Cell Mol Immunol 17, 193–202 (2020). https://doi.org/10.1038/s41423-020-0367-1

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