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

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.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Howden AJM,Hukelmann JL,Brenes A,Spinelli L,Sinclair LV,Lamond AI,Cantrell DA

doi

10.1038/s41590-019-0495-x

subject

Has Abstract

pub_date

2019-11-01 00:00:00

pages

1542-1554

issue

11

eissn

1529-2908

issn

1529-2916

pii

10.1038/s41590-019-0495-x

journal_volume

20

pub_type

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