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Integrative biology of T cell activation

Nature Immunology volume 15, pages 790–797 (2014)Cite this article

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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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Figure 1: Overview of the early TCR signal-transduction network.
Figure 2: Positive regulatory plug-ins of the Lat interactome.
Figure 3: Negative regulatory plug-ins present in the Lat interactome.
Figure 4: Lat nanoclusters and microclusters.

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  • 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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Authors and Affiliations

  1. Centre d'Immunologie de Marseille-Luminy, UM2 Aix-Marseille Université, Marseille, France

    Bernard Malissen, Claude Grégoire, Marie Malissen & Romain Roncagalli

  2. INSERM U1104, Marseille, France

    Bernard Malissen, Claude Grégoire, Marie Malissen & Romain Roncagalli

  3. CNRS UMR7280, Marseille, France

    Bernard Malissen, Claude Grégoire, Marie Malissen & Romain Roncagalli

  4. Centre d'Immunophénomique, UM2 Aix-Marseille Université, Marseille, France

    Bernard Malissen & Marie Malissen

  5. INSERM US012, Marseille, France

    Bernard Malissen & Marie Malissen

  6. CNRS UMS3367, Marseille, France

    Bernard Malissen & Marie Malissen

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Correspondence to Bernard Malissen.

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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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