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

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.
Romain Roncagalli # 1 2 3,  Simon Hauri # 4 5,  Fréderic Fiore 6 7 8,  Yinming Liang 1 2 3,  Zhi Chen 9,  Amandine Sansoni 6 7 8,  Kartiek Kanduri 9,  Rachel Joly 1 2 3,  Aurélie Malzac 1 2 3,  Harri Lähdesmäki 9 10,  Riitta Lahesmaa 9,  Sho Yamasaki 11,  Takashi Saito 12,  Marie Malissen 1 2 3,  Ruedi Aebersold 4 13,  Matthias Gstaiger 4 5,  Bernard Malissen 1 2 3 6 7 8
Affiliations

Affiliations

  • 1 Centre d'Immunologie de Marseille-Luminy, UM2 Aix-Marseille Université, Marseille, France.
  • 2 INSERM U1104, Marseille, France.
  • 3 CNRS UMR7280, Marseille, France.
  • 4 Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
  • 5 Competence Center for Systems Physiology and Metabolic Diseases, ETH Zurich, Switzerland.
  • 6 Centre d'Immunophénomique, UM2 Aix-Marseille Université, Marseille, France.
  • 7 INSERM US012, Marseille, France.
  • 8 CNRS UMS3367, Marseille, France.
  • 9 Turku Centre for Biotechnology, University of Turku and Abo Akademi University, Turku, Finland.
  • 10 Department of Information and Computer Science, Aalto University, Finland.
  • 11 Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
  • 12 RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan.
  • 13 Faculty of Science, University of Zurich, Zurich, Switzerland.
  • # Contributed equally.
PMID: 24584089 DOI: 10.1038/ni.2843
Abstract

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.

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