The cytotoxic T cell proteome and its shaping by the kinase mTOR

Nat Immunol. 2016 Jan;17(1):104-12. doi: 10.1038/ni.3314. Epub 2015 Nov 9.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Chromatography
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Immunoblotting
  • Male
  • Mass Spectrometry
  • Mechanistic Target of Rapamycin Complex 1
  • Mice
  • Multiprotein Complexes / immunology
  • Multiprotein Complexes / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Proteome / immunology*
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism*
  • TOR Serine-Threonine Kinases / immunology
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Multiprotein Complexes
  • Proteome
  • TOR Serine-Threonine Kinases
  • Mechanistic Target of Rapamycin Complex 1

Associated data

  • GEO/GSE70925