Quantitative analysis of T cell proteomes and environmental sensors during T cell differentiation.
Andrew J M HowdenJens L HukelmannAlejandro BrenesLaura SpinelliLinda V SinclairAngus I LamondDoreen A CantrellPublished in: Nature immunology (2019)
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.
Keyphrases
- cell cycle
- single cell
- induced apoptosis
- mass spectrometry
- cell cycle arrest
- dendritic cells
- regulatory t cells
- cell fate
- cell proliferation
- cell therapy
- high resolution
- type iii
- genome wide
- gene expression
- signaling pathway
- metabolic syndrome
- oxidative stress
- human health
- cell death
- peripheral blood
- low cost
- immune response
- mesenchymal stem cells
- pi k akt
- tandem mass spectrometry