A discrete subset of epigenetically primed human NK cells mediates antigen-specific immune responses

Victoria Stary, Ram Vinay Pandey, Johanna Strobl, Lisa Kleissl, Patrick Starlinger, David Pereyra, Wolfgang Weninger, Gottfried F Fischer, Christoph Bock, Matthias Farlik, Georg Stary

Research output: Journal article (peer-reviewed)Journal article

37 Citations (Scopus)

Abstract

Adaptive features of natural killer (NK) cells have been reported in various species with different underlying mechanisms. It is unclear, however, which NK cell populations are capable of mounting antigen-specific recall responses and how such functions are regulated at the molecular level. Here, we identify and characterize a discrete population of CD49a+CD16- NK cells in the human liver that displays increased epigenetic potential to elicit memory responses and has the functional properties to exert antigen-specific immunity in the skin as an effector site. Integrated chromatin-based epigenetic and transcriptomic profiling revealed unique characteristics of hepatic CD49a+CD16- NK cells when compared with conventional CD49a-CD16+ NK cells, thereby defining active genomic regions and molecules underpinning distinct NK cell reactivity. In contrast to conventional NK cells, our results suggest that adaptive CD49a+CD16- NK cells are able to bypass the KIR receptor-ligand system upon antigen-specific stimulation. Furthermore, these cells were highly migratory toward chemokine gradients expressed in epicutaneous patch test lesions as an effector site of adaptive immune responses in the skin. These results define pathways operative in human antigen-specific adaptive NK cells and provide a roadmap for harnessing this NK cell subset for specific therapeutic or prophylactic vaccine strategies.

Original languageEnglish
Article numbereaba6232
JournalScience immunology
Volume5
Issue number52
DOIs
Publication statusPublished - 16 Oct 2020
Externally publishedYes

Keywords

  • Adaptive Immunity/genetics
  • Adult
  • Aged
  • Aged, 80 and over
  • Biopsy
  • Cell Line, Tumor
  • Cell Separation
  • Dermatitis, Contact/genetics
  • Epigenesis, Genetic/immunology
  • Female
  • Flow Cytometry
  • Humans
  • Integrin alpha1/metabolism
  • Killer Cells, Natural/immunology
  • Liver/cytology
  • Lymphocyte Subsets/immunology
  • Male
  • Middle Aged
  • Nickel/administration & dosage
  • Patch Tests
  • Primary Cell Culture
  • RNA-Seq
  • Single-Cell Analysis
  • Skin/cytology

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