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

Andy J. M. Howden, Jens L. Hukelmann, Alejandro Brenes, Laura Spinelli, Linda V. Sinclair, Angus I. Lamond (Lead / Corresponding author), Doreen A. Cantrell (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)
49 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)1542-1554
Number of pages13
JournalNature Immunology
Volume20
Issue number11
Early online date7 Oct 2019
DOIs
Publication statusPublished - Nov 2019

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