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

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Voisinne, Guillaume | Kersse, Kristof | Chaoui, Karima | Lu, Liaoxun | Chaix, Julie | Zhang, Lichen | Goncalves Menoita, Marisa | Girard, Laura | Ounoughene, Youcef | Wang, Hui | Burlet-Schiltz, Odile | Luche, Hervé | Fiore, Frederic | Malissen, Marie | Peredo, Anne Gonzalez De | Liang, Yinming | Roncagalli, Romain | Malissen, Bernard

Edité par CCSD ; Nature Publishing Group -

International audience. he 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 gene­targeted mice, each expressing one tagged form of a canonical protein of the TCR­signaling 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 signal­transduction network comprises at least 277 unique proteins involved in 366 high­confidence 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.

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