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

Publié dans: Nat Immunol 2019 Nov; 20(11): 1530-1541

Auteurs: Voisinne G, Kersse K, Chaoui K, Lu L, Chaix J, Zhang L, Goncalves Menoita M, Girard L, Ounoughene Y, Wang H, Burlet-Schiltz O, Luche H, Fiore F, Malissen M, Gonzalez de Peredo A, Liang Y, Roncagalli R, Malissen B

Résumé

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.

Lien vers Pubmed [PMID] – 31591574

Lien vers le DOI – 10.1038/s41590-019-0489-8