Quantitative interactomics in primary T cells unveils TCR signal diversification extent and dynamics
Résumé
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.
Domaines
Immunologie
Origine : Publication financée par une institution