Abstract
The activation of T cells mediated by the T cell antigen receptor (TCR) requires the interaction of dozens of proteins, and its malfunction has pathological consequences. Our major focus is on new developments in the systems-level understanding of the TCR signal-transduction network. To make sense of the formidable complexity of this network, we argue that 'fine-grained' methods are needed to assess the relationships among a few components that interact on a nanometric scale, and those should be integrated with high-throughput '-omic' approaches that simultaneously capture large numbers of parameters. We illustrate the utility of this integrative approach with the transmembrane signaling protein Lat, which is a key signaling hub of the TCR signal-transduction network, as a connecting thread.
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Change history
25 August 2014
In the version of this article initially published, the page ranges for references 7 and 15 were missing. Those are 815-823 (ref. 7) and 808-814 (ref. 15). The error has been corrected in the HTML and PDF versions of the article.
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Acknowledgements
This paper is dedicated to the memory of François Kourilsky. We thank R. Germain and P. Bongrand for discussions. Supported by the Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Aix-Marseille Université, French National Infrastructure for Mouse Phenogenomics (PHENOMIN), Agence Nationale de Recherche (Basilic project to M.M.) and European Research Council (“Integrate” grant to B.M.).
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Malissen, B., Grégoire, C., Malissen, M. et al. Integrative biology of T cell activation. Nat Immunol 15, 790–797 (2014). https://doi.org/10.1038/ni.2959
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DOI: https://doi.org/10.1038/ni.2959
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