Cited by 231T-cell and B-cell ImmunologyAdvanced Proteomics Techniques and ApplicationsPI3K/AKT/mTOR signaling in cancer

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

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Howden, Andrew J. M., Hukelmann, Jens L., Brenes, Alejandro, Spinelli, Laura, Sinclair, Linda V., Lamond, Angus I., Cantrell, Doreen A.·2019·Nature Immunology

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.

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  • Naïve T cells express non-detectable levels of CDK8, which are upregulated upon T cell activation and differentiation.

    “Naïve T cells express non-detectable levels of CDK8, which are upregulated upon T cells activation and differentiation (Howden et al., 2019).”

    From CDK8 fine-tunes IL-6 transcriptional activities by limiting STAT3 resident time at the gene loci (2020) · cites this paper as Howden et al., 2019

    The Results section on cell-context effects of mTORC1 inhibition describes undetectable cyclin D3 and low CDK4/6 in naïve T cells, followed by increases after activation. Searches for CDK8 and cyclin-dependent kinase 8 found no passage in our copy stating that CDK8 is undetectable in naïve cells or upregulated with activation and differentiation. The available passages have no page numbers. (LLM, conf=0.74)

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Authors
Howden, A. J. M., Hukelmann, J. L., Brenes, A., Spinelli, L., Sinclair, L. V., Lamond, A. I., & Cantrell, D. A.
Affiliations
University of Dundee (GB)
Corresponding author
  • Lamond, Angus I.
  • Cantrell, Doreen A.
Venue
Nature Immunology
Published
2019-10-07
Volume
20
Issue
11
Pages
1542-1554
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
OpenAlex
W2977451996
Cited by
231
References
49
Citations by year
2026: 19 · 2025: 34 · 2024: 42 · 2023: 34 · 2022: 34 · 2021: 37 · 2020: 29 · 2019: 2
FWCI
10.19
Type
journal article
Language
en
Open access
Locations
  • Nature Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Discovery Research Portal (University of Dundee) (submittedVersion, other-oa)
Funders
Wellcome Trust (205023/Z/16/Z, 105024/Z/14/Z, 202950/Z/16/Z)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Keywords
T cell proteome, CD4+ T cells, CD8+ T cells, mTORC1, T cell differentiation, naive T cells, effector T cells, protein copy number, nutrient sensing, T cell metabolism, cell cycle progression, immune activation, quantitative mass spectrometry
MeSH terms
Mechanistic Target of Rapamycin Complex 1, Animals, Cell Differentiation, Cells, Cultured, Female, Gene Expression Regulation, Male, Mice, Transgenic, Mass Spectrometry, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Gene Dosage, Sirolimus, Proteome, Gene Expression Profiling, Proteomics, Mice, Cell Cycle Checkpoints

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