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

摘要

T cell antigen receptor (TCR)-mediated T cell activation requires the interaction of dozens of proteins. 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 forming around the kinase Zap70 and the adaptors Lat and SLP-76. Most of the 112 high confidence time-resolved protein interactions we observed were novel. The CD6 surface receptor was found capable of initiating its own signaling pathway by recruiting SLP-76 and Vav1, irrespective of the presence of Lat. Our findings provide a more complete model of TCR signaling in which CD6 constitutes a signaling hub contributing to TCR signal diversification.