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

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

Roncagalli R#1,2,3, Hauri S#4,5, Fiore F6,7,8, Liang Y1,2,3, Chen Z9, Sansoni A6,7,8, Kanduri K9, Joly R1,2,3, Malzac A1,2,3, Lähdesmäki H9,10, Lahesmaa R9, Yamasaki S11, Saito T12, Malissen M1,2,3, Aebersold R4,13, Gstaiger M4,5, Malissen B1,2,3,6,7,8.

Author information

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

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.

PMID:
24584089
PMCID:
PMC4037560
DOI:
10.1038/ni.2843
[Indexed for MEDLINE]
Free PMC Article

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