T细胞分化过程中蛋白质组和环境感受器的定量分析，这一成果由英国邓迪大学Doreen A. Cantrell和Angus I. Lamond等研究人员合作取得。2019年10月7日，《自然—免疫学》杂志在线发表了该研究成果。

通过定量质谱分析，研究人员揭示了CD4阳性和CD8阳性T细胞如何重塑蛋白质组以响应抗原和哺乳动物雷帕霉素靶标复合物1（mTORC1）。分析每个细胞中超过9000种蛋白质的拷贝数可提供对T细胞表型的新认识，从而揭示了影响T细胞命运的代谢和蛋白质合成机制以及环境传感器。

研究人员揭示了淋巴细胞环境感应是由免疫激活控制的，并且CD4阳性和CD8阳性T细胞在其固有的营养转运和生物合成能力方面有所不同。这些数据还揭示了对初始T细胞与效应T细胞中mTORC1进行抑制所产生的相同和不同结果：mTORC1抑制会损害活化的初始细胞而非效应细胞中的细胞周期进程，而新陈代谢在这两个群体中均受到影响。

这项研究提供了初始和效应T细胞蛋白质组的全面图谱，以及探索和理解T细胞表型和mTORC1功能的资源。

附：英文原文

Title: Quantitative analysis of T cell proteomes and environmental sensors during T cell differentiation

Author: Andrew J. M. Howden, Jens L. Hukelmann, Alejandro Brenes, Laura Spinelli, Linda V. Sinclair, Angus I. Lamond, Doreen A. Cantrell

Issue&Volume: 2019-10-07

Abstract: 

Quantitative mass spectrometry reveals how CD4+ and CD8+ T cells restructure proteomes in response to antigen and mammalian target of rapamycin complex 1 (mTORC1). Analysis of copy numbers per cell of >9,000 proteins provides new understanding of T cell phenotypes, exposing the metabolic and protein synthesis machinery and environmental sensors that shape T cell fate. We reveal that lymphocyte environment sensing is controlled by immune activation, and that CD4+ and CD8+ T cells differ in their intrinsic nutrient transport and biosynthetic capacity. Our data also reveal shared and divergent outcomes of mTORC1 inhibition in naïve versus effector T cells: mTORC1 inhibition impaired cell cycle progression in activated naïve cells, but not effector cells, whereas metabolism was consistently impacted in both populations. This study provides a comprehensive map of naïve and effector T cell proteomes, and a resource for exploring and understanding T cell phenotypes and cell context effects of mTORC1.

DOI: 10.1038/s41590-019-0495-x

Source: https://www.nature.com/articles/s41590-019-0495-x