Mammalian Target of Rapamycin shapes the cytotoxic T cell proteome

High resolution mass spectrometry maps the CD8 cytotoxic cell (CTL) proteome and the impact of mammalian target of rapamycin complex 1 (mTORC1) on CTL. We show mTORC1 selectively represses and promotes expression of a subset (10%) of CTL proteins including key CTL effector and adhesion molecules and adaptor proteins. mTORC1 also controls flux through a selective subset of metabolic pathways but is not an on/off switch for CTL metabolism. Proteomic data highlighted the potential for mTORC1 negative control of phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P3) production in CTL. Further work revealed that mTORC1 represses PI(3,4,5)P3 production and controls the mTORC2 requirement for activation of the serine/threonine kinase AKT. Unbiased proteomic analysis thus provides a comprehensive understanding of CTL identity and mTORC1 control of CTL function.