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Signaling from T cell receptors (TCRs) and chimeric antigen receptors (CARs) on T cells

Cellular & Molecular Immunology volume 17, pages 600–612 (2020)Cite this article

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Abstract

T cells react to foreign or self-antigens through T cell receptor (TCR) signaling. Several decades of research have delineated the mechanism of TCR signal transduction and its impact on T cell performance. This knowledge provides the foundation for chimeric antigen receptor T cell (CAR-T cell) technology, by which T cells are redirected in a major histocompatibility complex-unrestricted manner. TCR and CAR signaling plays a critical role in determining the T cell state, including exhaustion and memory. Given its artificial nature, CARs might affect or rewire signaling differently than TCRs. A better understanding of CAR signal transduction would greatly facilitate improvements to CAR-T cell technology and advance its usefulness in clinical practice. Herein, we systematically review the knowns and unknowns of TCR and CAR signaling, from the contact of receptors and antigens, proximal signaling, immunological synapse formation, and late signaling outcomes. Signaling through different T cell subtypes and how signaling is translated into practice are also discussed.

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  1. Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore, 117545, Singapore

    Ling Wu, Qianru Wei, Joanna Brzostek & Nicholas R. J. Gascoigne

  2. Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore, Singapore

    Nicholas R. J. Gascoigne

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Wu, L., Wei, Q., Brzostek, J. et al. Signaling from T cell receptors (TCRs) and chimeric antigen receptors (CARs) on T cells. Cell Mol Immunol 17, 600–612 (2020). https://doi.org/10.1038/s41423-020-0470-3

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