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Quantitative analysis of T cell proteomes and environmental sensors during T cell differentiation
Open accessAbstract
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 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
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Metadata
- 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
- Venue
- Nature Immunology
- Published
- 2019-10-07
- Volume
- 20
- Issue
- 11
- Pages
- 1542-1554
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- 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
- 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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