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

Kristen N. Pollizzi, Im Hong Sun, Chirag H. Patel, Ying Chun Lo, Min Hee Oh, Adam T. Waickman, Ada J. Tam, Richard L. Blosser, Jiayu Wen, Greg M. Delgoffe, Jonathan Powell

Research output: Contribution to journalArticle

Abstract

The asymmetric partitioning of fate-determining proteins has been shown to contribute to the generation of CD8+ effector and memory T cell precursors. Here we demonstrate the asymmetric partitioning of mTORC1 activity after the activation of naive CD8+ T cells. This results in the generation of two daughter T cells, one of which shows increased mTORC1 activity, increased glycolytic activity and increased expression of effector molecules. The other daughter T cell has relatively low mTORC1 activity and increased lipid metabolism, expresses increased amounts of anti-apoptotic molecules and subsequently displays enhanced long-term survival. Mechanistically, we demonstrate a link between T cell antigen receptor (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.

Original languageEnglish (US)
JournalNature Immunology
DOIs
StateAccepted/In press - Apr 11 2016

ASJC Scopus subject areas

  • Immunology

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    Pollizzi, K. N., Sun, I. H., Patel, C. H., Lo, Y. C., Oh, M. H., Waickman, A. T., Tam, A. J., Blosser, R. L., Wen, J., Delgoffe, G. M., & Powell, J. (Accepted/In press). Asymmetric inheritance of mTORC1 kinase activity during division dictates CD8+ T cell differentiation. Nature Immunology. https://doi.org/10.1038/ni.3438