Lysosomal NKG7 restrains mTORC1 activity to promote CD8⁺ T cell durability and tumor control.

ABSTRACT: During infection and cancer, mTORC1-mediated metabolic regulation impacts CD8⁺ T cell effector expansion and memory development. However, the mechanisms by which CD8⁺ T cells regulate mTORC1 to support their unique metabolic requirements remain unknown. Here we show that NKG7, a lysosomal protein whose expression is restricted to cytotoxic lymphocytes, negatively regulates mTORC1 recruitment and activation by inhibiting assembly and function of the lysosomal proton pump, vacuolar ATPase (v-ATPase). Human and mouse CD8⁺ T cells lacking NKG7 show more acidic lysosomes and increased activation of mTORC1 signaling, which could be reversed by inhibition of v-ATPase activity. In mice responding to LCMV infection, NKG7-deleted effector CD8⁺ T cells are

SUBMITTER: Ham H 

PROVIDER: S-EPMC11829009 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature