Asymmetric inheritance of mTORC1 kinase activity during division dictates CD8 T cell differentiation

The asymmetric partitioning of fate determining proteins has been shown to contribute to the generation of effector and memory CD8(+) T cell precursors. Here, we demonstrate the asymmetric partitioning of mTORC1 activity upon activation of naïve CD8(+) T cells. This results in the generation of one daughter T cell with increased mTORC1 activity, increased glycolytic activity and increased expression of effector molecules. The other daughter T cell inherits relatively low levels of mTORC1 activity, possesses increased lipid metabolism, expresses increased anti-apoptotic molecules and subsequently displays enhanced long-term survival. Mechanistically, we demonstrate a link between TCR-induced asymmetric expression of amino acid transporters and RagC-mediated translocation of mTOR to the lysosomes. Overall, our data provide important insight into how mTORC1-mediated metabolic reprogramming affects the fate decisions of T cells.