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研究揭示TCR信号的多样性和动力学
作者:小柯机器人 发布时间:2019/10/8 15:22:48

法国艾克斯马赛大学Bernard Malissen、Romain Roncagalli和中国新乡医科大学梁银明研究组合作发现,T细胞定量互作揭示了T细胞抗原受体(TCR)信号的多样化程度和动态变化。该项研究成果在线发表于2019年10月7日的《自然—免疫学》。

他们从15只靶向基因的小鼠中分离了原代CD4 + T细胞,每只小鼠均表达一种TCR信号通路经典蛋白的标记形式。使用亲和纯化与质谱联用,他们分析了在600s TCR参与下每个标记蛋白周围组装的信号小体的组成和动力学。他们表明,TCR信号转导网络包含至少277种参与366个高可信度相互作用的独特蛋白质,并且TCR信号在质膜水平上表现出广泛多样化。整合相互作用蛋白的细胞丰度及其相互作用化学计量,可提供每种已记录相互作用的定量和背景信息,从而可以预期单个相互作用蛋白的消融是否会影响整个TCR信号转导网络。

据介绍,TCR激活T细胞导致形成信号蛋白复合物(信号体),其组成尚未在系统水平上进行分析。

附:英文原文

Title: Quantitative interactomics in primary T cells unveils TCR signal diversification extent and dynamics

Author: Guillaume Voisinne, Kristof Kersse, Karima Chaoui, Liaoxun Lu, Julie Chaix, Lichen Zhang, Marisa Goncalves Menoita, Laura Girard, Youcef Ounoughene, Hui Wang, Odile Burlet-Schiltz, Herv Luche, Frdric Fiore, Marie Malissen, Anne Gonzalez de Peredo, Yinming Liang, Romain Roncagalli, Bernard Malissen

Issue&Volume: 2019-10-07

Abstract: 

The activation of T cells by the T cell antigen receptor (TCR) results in the formation of signaling protein complexes (signalosomes), the composition of which has not been analyzed at a systems level. Here, we isolated primary CD4+ T cells from 15 gene-targeted mice, each expressing one tagged form of a canonical protein of the TCR-signaling pathway. Using affinity purification coupled with mass spectrometry, we analyzed the composition and dynamics of the signalosomes assembling around each of the tagged proteins over 600 s of TCR engagement. We showed that the TCR signal-transduction network comprises at least 277 unique proteins involved in 366 high-confidence interactions, and that TCR signals diversify extensively at the level of the plasma membrane. Integrating the cellular abundance of the interacting proteins and their interaction stoichiometry provided a quantitative and contextual view of each documented interaction, permitting anticipation of whether ablation of a single interacting protein can impinge on the whole TCR signal-transduction network.

DOI: 10.1038/s41590-019-0489-8

Source: https://www.nature.com/articles/s41590-019-0489-8

期刊信息

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:23.53
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex