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Insights into the initiation of TCR signaling

Abstract

The initiation of T cell antigen receptor signaling is a key step that can result in T cell activation and the orchestration of an adaptive immune response. Early events in T cell receptor signaling can distinguish between agonist and endogenous ligands with exquisite selectivity, and show extraordinary sensitivity to minute numbers of agonists in a sea of endogenous ligands. We review our current knowledge of models and crucial molecules that aim to provide a mechanistic explanation for these observations. Building on current understanding and a discussion of unresolved issues, we propose a molecular model for initiation of T cell receptor signaling that may serve as a useful guide for future studies.

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Figure 1: Schematic depiction of kinetic proofreading.
Figure 2: Schematic representation of the mechanosensor model of TCR signal initiation.
Figure 3: The regulation of Lck by phosphorylation.
Figure 4: TCR activation as a consequence of the combined relocalization of CD4 and CD8 coreceptors and bound Lck.

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Acknowledgements

We thank M. Fruschicheva for help with the references. We also thank K. Vicari of the Nature Publishing Group for her artistic work on the figures in this article. This work was supported, in part, by a grant from the US National Institutes of Health (PO1 AI091580 to A.K.C. and A.W.).

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Chakraborty, A., Weiss, A. Insights into the initiation of TCR signaling. Nat Immunol 15, 798–807 (2014). https://doi.org/10.1038/ni.2940

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