Cutting Edge: IL-2–Induced Expression of the Amino Acid Transporters SLC1A5 and CD98 Is a Prerequisite for NKG2D-Mediated Activation of Human NK Cells

  • Jensen H
  • Potempa M
  • Gotthardt D
  • et al.
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Abstract

Priming of human NK cells with IL-2 is necessary to render them functionally competent upon NKG2D engagement. We examined the underlying mechanisms that control NKG2D responsiveness in NK cells and found that IL-2 upregulates expression of the amino acid transporters SLC1A5 and CD98. Using specific inhibitors to block SLC1A5 and CD98 function, we found that production of IFN-γ and degranulation by CD56bright and CD56dim NK cells following NKG2D stimulation were dependent on both transporters. IL-2 priming increased the activity of mTORC1, and inhibition of mTORC1 abrogated the ability of the IL-2–primed NK cells to produce IFN-γ in response to NKG2D-mediated stimulation. This study identifies a series of IL-2–induced cellular changes that regulates the NKG2D responsiveness in human NK cells.

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Jensen, H., Potempa, M., Gotthardt, D., & Lanier, L. L. (2017). Cutting Edge: IL-2–Induced Expression of the Amino Acid Transporters SLC1A5 and CD98 Is a Prerequisite for NKG2D-Mediated Activation of Human NK Cells. The Journal of Immunology, 199(6), 1967–1972. https://doi.org/10.4049/jimmunol.1700497

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