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Nat Immunol. 2019 Oct 7. doi: 10.1038/s41590-019-0489-8. [Epub ahead of print]

Quantitative interactomics in primary T cells unveils TCR signal diversification extent and dynamics.

Author information

1
Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, Marseille, France.
2
Institut de Pharmacologie et de Biologie Structurale, Département Biologie Structurale Biophysique, Protéomique Génopole Toulouse Midi Pyrénées CNRS UMR 5089, Toulouse, France.
3
School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, China.
4
Laboratory of Mouse Genetics, Institute of Psychiatry and Neuroscience, Xinxiang Medical University, Xinxiang, China.
5
Centre d'Immunophénomique, Aix Marseille Université, INSERM, CNRS UMR, Marseille, France.
6
Laboratory of Immunophenomics, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, China.
7
School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, China. yinming.liang@foxmail.com.
8
Laboratory of Immunophenomics, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, China. yinming.liang@foxmail.com.
9
Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, Marseille, France. roncagalli@ciml.univ-mrs.fr.
10
Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, Marseille, France. bernardm@ciml.univ-mrs.fr.
11
Centre d'Immunophénomique, Aix Marseille Université, INSERM, CNRS UMR, Marseille, France. bernardm@ciml.univ-mrs.fr.
12
Laboratory of Immunophenomics, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, China. bernardm@ciml.univ-mrs.fr.

Abstract

The activation of T cells by the T cell antigen receptor (TCR) results in the formation of signaling protein complexes (signalosomes), the composition of which has not been analyzed at a systems level. Here, we isolated primary CD4+ T cells from 15 gene-targeted mice, each expressing one tagged form of a canonical protein of the TCR-signaling pathway. Using affinity purification coupled with mass spectrometry, we analyzed the composition and dynamics of the signalosomes assembling around each of the tagged proteins over 600 s of TCR engagement. We showed that the TCR signal-transduction network comprises at least 277 unique proteins involved in 366 high-confidence interactions, and that TCR signals diversify extensively at the level of the plasma membrane. Integrating the cellular abundance of the interacting proteins and their interaction stoichiometry provided a quantitative and contextual view of each documented interaction, permitting anticipation of whether ablation of a single interacting protein can impinge on the whole TCR signal-transduction network.

PMID:
31591574
DOI:
10.1038/s41590-019-0489-8

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