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

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 naive versus effector T cells: mTORC1 inhibition impaired cell cycle progression in activated naive cells, but not effector cells, whereas metabolism was consistently impacted in both populations. This study provides a comprehensive map of naive and effector T cell proteomes, and a resource for exploring and understanding T cell phenotypes and cell context effects of mTORC1. Cantrell and colleagues perform a comparative quantitative mass spectrometric analysis of the proteomes of naive and activated CD4+ and CD8+ T cells. Proteomes are dynamically regulated and mTORC1 inhibition leads to differential consequences depending on cell state.