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

Romain Roncagalli; Simon Hauri; Fréderic Fiore; Yinming Liang; Zhi Chen; Amandine Sansoni; Kartiek Kanduri; Rachel Joly; Aurélie Malzac; Harri Lähdesmäki; Riitta Lahesmaa; Sho Yamasaki; Takashi Saito; Marie Malissen; Ruedi Aebersold; Matthias Gstaiger; Bernard Malissen

doi:10.1038/ni.2843

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

Romain Roncagalli, Simon Hauri, Fréderic Fiore, Yinming Liang, Zhi Chen, Amandine Sansoni, Kartiek Kanduri, Rachel Joly, Aurélie Malzac, Harri Lähdesmäki, Riitta Lahesmaa, Sho Yamasaki, Takashi Saito, Marie Malissen, Ruedi Aebersold, Matthias Gstaiger, Bernard Malissen

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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.

Original language	English
Pages (from-to)	384-392
Number of pages	9
Journal	Nature Immunology
Volume	15
Issue number	4
DOIs	https://doi.org/10.1038/ni.2843
Publication status	Published - Apr 2014

All Science Journal Classification (ASJC) codes

Immunology and Allergy
Immunology

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Roncagalli, R., Hauri, S., Fiore, F., Liang, Y., Chen, Z., Sansoni, A., Kanduri, K., Joly, R., Malzac, A., Lähdesmäki, H., Lahesmaa, R., Yamasaki, S., Saito, T., Malissen, M., Aebersold, R., Gstaiger, M., & Malissen, B. (2014). Quantitative proteomics analysis of signalosome dynamics in primary T cells identifies the surface receptor CD6 as a Lat adaptor-independent TCR signaling hub. Nature Immunology, 15(4), 384-392. https://doi.org/10.1038/ni.2843

Roncagalli, R, Hauri, S, Fiore, F, Liang, Y, Chen, Z, Sansoni, A, Kanduri, K, Joly, R, Malzac, A, Lähdesmäki, H, Lahesmaa, R, Yamasaki, S, Saito, T, Malissen, M, Aebersold, R, Gstaiger, M & Malissen, B 2014, 'Quantitative proteomics analysis of signalosome dynamics in primary T cells identifies the surface receptor CD6 as a Lat adaptor-independent TCR signaling hub', Nature Immunology, vol. 15, no. 4, pp. 384-392. https://doi.org/10.1038/ni.2843

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

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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AU - Liang, Yinming

AU - Chen, Zhi

AU - Sansoni, Amandine

AU - Kanduri, Kartiek

AU - Joly, Rachel

AU - Malzac, Aurélie

AU - Lähdesmäki, Harri

AU - Lahesmaa, Riitta

AU - Yamasaki, Sho

AU - Saito, Takashi

AU - Malissen, Marie

AU - Aebersold, Ruedi

AU - Gstaiger, Matthias

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

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