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

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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

DOI 10.1038/s41590-019-0495-xPMC PMC6859072

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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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Paradox Found: Global Accounting of Lymphocyte Protein SynthesisPreprint
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Author Response: Paradox Found: Global Accounting of Lymphocyte Protein Synthesis
Seedhom, M. O., Dersh, D., Hollý, J., Pavon-Eternod, M., Wei, J., Angel, M., Shores, L. S., David, A., Santos, J. J. D. S., Hickman, H. D., et al. (2024) · eLife · doi:10.7554/elife.89015.2.sa4
eLife Assessment: Paradox Found: Global Accounting of Lymphocyte Protein Synthesis
Belz, G. T. (2024) · eLife · doi:10.7554/elife.89015.2.sa3
Reviewer #3 (Public Review): Paradox Found: Global Accounting of Lymphocyte Protein Synthesis
(2024) · eLife · doi:10.7554/elife.89015.2.sa0
Reviewer #1 (Public Review): Paradox Found: Global Accounting of Lymphocyte Protein Synthesis
(2024) · eLife · doi:10.7554/elife.89015.2.sa2
Reviewer #2 (Public Review): Paradox Found: Global Accounting of Lymphocyte Protein Synthesis
(2024) · eLife · doi:10.7554/elife.89015.2.sa1
eLife Assessment: Proteomic and functional comparison between human induced and embryonic stem cells
Kornmann, B. (2024) · eLife · doi:10.7554/elife.92025.1.sa3
None: Proteomic and functional comparison between human induced and embryonic stem cells
Brenes, A. J., Griesser, E., Sinclair, L. V., Davidson, L., Prescott, A. R., Singh, F., Hogg, E. K. J., Espejo-Serrano, C., Jiang, H., Yoshikawa, H., et al. (2024) · eLife · doi:10.7554/elife.92025.1.sa4
Self-citation
PIM kinase control of CD8 T cell protein synthesis and cell traffickingPreprint
Marchingo, J. M., Spinelli, L., Pathak, S., & Cantrell, D. A. (2024) · eLife · doi:10.7554/elife.98622.1
Self-citation

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.
ORCID: Howden, Andrew J. M.
Hukelmann, Jens L.
Brenes, Alejandro
Spinelli, Laura
Sinclair, Linda V.
Lamond, Angus I.
Cantrell, Doreen A.
Venue: Nature Immunology
Publisher: Springer Science and Business Media LLC
Published: 2019-10-07
Volume: 20
Issue: 11
Pages: 1542-1554
ISSN: 1529-2908 (ISSN-L)
1529-2916
DOI: 10.1038/s41590-019-0495-x
PMC: PMC6859072
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: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
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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Quantitative analysis of T cell proteomes and environmental sensors during T cell differentiation

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