Quantitative proteomics analysis of signalosome dynamics in primary T cells identifies the surface receptor CD6 as a Lat adaptor-independent TCR signaling hub

Nat Immunol. 2014 Apr;15(4):384-392. doi: 10.1038/ni.2843. Epub 2014 Mar 2.


T cell antigen receptor (TCR)-mediated activation of T cells requires the interaction of dozens of proteins. Here we used quantitative mass spectrometry and activated primary CD4(+) T cells from mice in which a tag for affinity purification was knocked into several genes to determine the composition and dynamics of multiprotein complexes that formed around the kinase Zap70 and the adaptors Lat and SLP-76. Most of the 112 high-confidence time-resolved protein interactions we observed were previously unknown. The surface receptor CD6 was able to initiate its own signaling pathway by recruiting SLP-76 and the guanine nucleotide-exchange factor Vav1 regardless of the presence of Lat. Our findings provide a more complete model of TCR signaling in which CD6 constitutes a signaling hub that contributes to the diversification of TCR signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Antigens, CD / metabolism*
  • Antigens, Differentiation, T-Lymphocyte / metabolism*
  • CD4-Positive T-Lymphocytes / immunology*
  • Calcium Signaling / genetics
  • Cells, Cultured
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Multiprotein Complexes / metabolism
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Protein Binding / genetics
  • Proteomics
  • Proto-Oncogene Proteins c-vav / metabolism
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocyte Subsets / immunology*
  • ZAP-70 Protein-Tyrosine Kinase / metabolism


  • Adaptor Proteins, Signal Transducing
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD6 antigen
  • Lat protein, mouse
  • Membrane Proteins
  • Multiprotein Complexes
  • Phosphoproteins
  • Proto-Oncogene Proteins c-vav
  • Receptors, Antigen, T-Cell
  • SLP-76 signal Transducing adaptor proteins
  • Vav1 protein, mouse
  • ZAP-70 Protein-Tyrosine Kinase
  • Zap70 protein, mouse

Associated data

  • GEO/GSE49507