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

Helle Jensen; Marc Potempa; Dagmar Gotthardt; Lewis L Lanier

doi:10.4049/jimmunol.1700497

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

J Immunol. 2017 Sep 15;199(6):1967-1972. doi: 10.4049/jimmunol.1700497. Epub 2017 Aug 7.

Authors

Helle Jensen¹, Marc Potempa¹, Dagmar Gotthardt^{1

2}, Lewis L Lanier^{3

2}

Affiliations

¹ Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143; and.
² Parker Institute for Cancer Immunotherapy, San Francisco, CA 94143.
³ Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143; and lewis.lanier@ucsf.edu.

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 CD56^bright and CD56^dim 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.

MeSH terms

Amino Acid Transport System ASC / genetics
Amino Acid Transport System ASC / metabolism*
CD56 Antigen / metabolism
Cells, Cultured
Cytotoxicity, Immunologic
Fusion Regulatory Protein-1 / metabolism*
Humans
Interferon-gamma / metabolism
Interleukin-2 / immunology
Interleukin-2 / metabolism
Killer Cells, Natural / physiology*
Lymphocyte Activation
Mechanistic Target of Rapamycin Complex 1
Minor Histocompatibility Antigens / genetics
Minor Histocompatibility Antigens / metabolism*
Multiprotein Complexes / antagonists & inhibitors
NK Cell Lectin-Like Receptor Subfamily K / metabolism
TOR Serine-Threonine Kinases / antagonists & inhibitors

Substances

Amino Acid Transport System ASC
CD56 Antigen
Fusion Regulatory Protein-1
Interleukin-2
KLRK1 protein, human
Minor Histocompatibility Antigens
Multiprotein Complexes
NK Cell Lectin-Like Receptor Subfamily K
SLC1A5 protein, human
Interferon-gamma
Mechanistic Target of Rapamycin Complex 1
TOR Serine-Threonine Kinases

Abstract

MeSH terms

Substances

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