LymphoAtlas: a dynamic and integrated phosphoproteomic resource of TCR signaling in primary T cells reveals ITSN2 as a regulator of effector functions

Mol Syst Biol. 2020 Jul;16(7):e9524. doi: 10.15252/msb.20209524.


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 after TCR stimulation. 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 after TCR engagement. Among proteins whose phosphorylation was regulated by TCR stimulation, we demonstrated, using a fast-track gene inactivation approach in primary lymphocytes, that the ITSN2 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:

Keywords: ITSN2; LymphoAtlas; TCR signaling network; dynamic biological processes; phosphoproteomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / metabolism*
  • Animals
  • Antibodies / pharmacology
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / immunology
  • Chromatography, Liquid
  • Computational Biology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred C57BL
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Protein Biosynthesis / drug effects
  • Protein Biosynthesis / genetics
  • Protein Biosynthesis / immunology
  • Protein Kinases / metabolism*
  • Proteomics*
  • Receptors, Antigen, T-Cell / metabolism*
  • Signal Transduction / genetics*
  • Signal Transduction / immunology
  • Tandem Mass Spectrometry
  • Time Factors


  • Adaptor Proteins, Vesicular Transport
  • Antibodies
  • Phosphoproteins
  • Receptors, Antigen, T-Cell
  • Protein Kinases