The cytotoxic T cell proteome and its shaping by the kinase mTOR
Open accessAbstract
We used high-resolution mass spectrometry to map the cytotoxic T lymphocyte (CTL) proteome and the effect of the metabolic checkpoint kinase mTORC1 on CTLs. The CTL proteome was dominated by metabolic regulators and granzymes, and mTORC1 selectively repressed and promoted expression of a subset of CTL proteins (~10%). These included key CTL effector molecules, signaling proteins and a subset of metabolic enzymes. Proteomic data highlighted the potential for negative control of the production of phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3) by mTORC1 in CTLs. mTORC1 repressed PtdIns(3,4,5)P3 production and determined the requirement for mTORC2 in activation of the kinase Akt. Our unbiased proteomic analysis thus provides comprehensive understanding of CTL identity and the control of CTL function by mTORC1.
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Previous studies have revealed poor mRNA-protein correlation in T cells regardless of functional status.
“Previous studies have revealed poor mRNA–protein correlation in T cells regardless of functional status23–25”
From Proteotoxic stress response drives T cell exhaustion and immune evasion (2025) · cites this paper as [23]
The section “A comparison of the CTL transcriptome and proteome” reports a moderate positive mRNA–protein correlation in cytotoxic T lymphocytes, supporting the claim of imperfect correspondence. It does not establish that this holds for T cells regardless of functional status; the cited analysis is limited to CTLs. Page numbers are unavailable in our copy. (LLM, conf=0.87)
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The Immunological Proteome Resource
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Extracellular signal-regulated kinase (ERK) pathway control of CD8+ T cell differentiation
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Modified Hypoxia-Inducible Factor Expression in CD8+ T Cells Increases Antitumor Efficacy
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- Authors
- Hukelmann, J. L., Anderson, K. E., Sinclair, L. V., Grzes, K. M., Murillo, A. B., Hawkins, P. T., Stephens, L. R., Lamond, A. I., & Cantrell, D. A.
- Affiliations
- University of Dundee (GB)
- Babraham Institute (GB)
- Corresponding author
- Cantrell, Doreen A
- ORCID
- Venue
- Nature Immunology
- Published
- 2015-11-09
- Volume
- 17
- Issue
- 1
- Pages
- 104-112
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC4685757
- OpenAlex
- W2191096966
- Semantic Scholar
- f09067c9976f2a9e24edeb52284d6302ec58001a
- Cited by
- 249
- References
- 50
- Citations by year
- 2026: 10 · 2025: 19 · 2024: 31 · 2023: 24 · 2022: 20 · 2021: 29 · 2020: 24 · 2019: 21 · 2018: 27 · 2017: 26 · 2016: 17 · 2015: 1
- FWCI
- 10.28
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (acceptedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Wellcome Trust (073980, 097418/Z/11/Z, 065975, /Z/11/Z, 105024, 105024/Z/14/Z, 097945/C/11/Z, 097418, 093713/Z/10/A, 073980/Z/03/Z, 093713)
- Biotechnology and Biological Sciences Research Council (BBS/E/B/000C0415, BBS/E/B/000C0413)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- cytotoxic T lymphocytes, mTORC1, mTORC2, Akt signaling, phosphatidylinositol 3,4,5-trisphosphate, granzymes, metabolic regulation, CD8+ T cell activation, T cell effector function
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Animals, Cells, Cultured, Chromatography, Enzyme-Linked Immunosorbent Assay, Female, Male, Mass Spectrometry, T-Lymphocytes, Cytotoxic, Immunoblotting, Oligonucleotide Array Sequence Analysis, Proteome, Multiprotein Complexes, Mice, TOR Serine-Threonine Kinases
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