LymphoAtlas: a dynamic and integrated phosphoproteomic resource ofTCRsignaling in primary T cells revealsITSN2 as a regulator of effector functions

T-cell receptor (TCR) ligation-mediated protein phosphorylation regulates the activation, cellular responses, and fates of T cells. Here, we used time-resolved high-resolution phosphoproteomics to identify, quantify, and characterize the phosphorylation dynamics of thousands of phosphorylation sites in primary T cells during the first 10 min afterTCRstimulation. Bioinformatic analysis of the data revealed a coherent orchestration of biological processes underlying T-cell activation. In particular, functional modules associated with cytoskeletal remodeling, transcription, translation, and metabolic processes were mobilized within seconds afterTCRengagement. Among proteins whose phosphorylation was regulated byTCRstimulation, we demonstrated, using a fast-track gene inactivation approach in primary lymphocytes, that theITSN2 adaptor protein regulated T-cell effector functions. This resource, called LymphoAtlas, represents an integrated pipeline to further decipher the organization of the signaling network encoding T-cell activation. LymphoAtlas is accessible to the community at: .