Defining the T cell proteome and the role of mTORC1 during differentiation using quantitative proteomics

High-resolution quantitative mass-spectrometry reveals similarities and disparities in how murine naïve CD4 and CD8 T cells respond to immune activation and re-structure proteomes as they differentiate to effector cells. The data map core transcriptional, metabolic and protein synthesis machinery, nutrient transporters and environment sensing molecules and reveal differences in the biosynthetic capacity of CD4 and CD8 T cells. One key nutrient sensing kinase is mammalian target of rapamycin complex1 (mTORC1). The current study identifies common and distinct mTORC1 regulated processes and divergent outcomes of mTORC1 inhibition in naïve versus effector CD4 and CD8 T cell populations. The data provide a resource that maps how immune activation and mTORC1 reshape CD4 and CD8 T cell proteomes and highlights that a deep understanding of T cell phenotype requires modelling of the impact of immune regulators on protein copy number, cellular protein concentrations and the subunit stoichiometry of key protein complexes.