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 D. Powell

Research output: Contribution to journalArticlepeer-review

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)
Pages (from-to)704-711
Number of pages8
JournalNature Immunology
Volume17
Issue number6
DOIs
StatePublished - May 19 2016

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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