Quantitative analysis of T cell proteomes and environmental sensors during T cell differentiation

Quantitative mass spectrometry reveals how CD4(+) and CD8(+) T cells re-structure proteomes in response to antigen and mammalian target of rapamycin complex 1 (mTORC1). Analysis of copy numbers per cell of >9000 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 was controlled by immune activation and that CD4(+) and CD8(+) T cells differed in their intrinsic nutrient transport and biosynthetic capacity. The data also revealed 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.