Interactions Between KIR3DS1 and HLA-F Activate Natural Killer Cells to Control HCV Replication in Cell Culture

Gastroenterology. 2018 Nov;155(5):1366-1371.e3. doi: 10.1053/j.gastro.2018.07.019. Epub 2018 Jul 19.

Abstract

Killer-cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer (NK) cells. Binding of KIR3DS1 to its recently discovered ligand, HLA-F, activates NK cells and has been associated with resolution of hepatitis C virus (HCV) infection. We investigated the mechanisms by which KIR3DS1 contributes to the antiviral immune response. Using cell culture systems, mice with humanized livers, and primary liver tissue from HCV-infected individuals, we found that the KIR3DS1 ligand HLA-F is up-regulated on HCV-infected cells, and that interactions between KIR3DS1 and HLA-F contribute to NK cell-mediated control of HCV. Strategies to promote interaction between KIR3DS1 and HLA-F might be developed for treatment of infectious diseases and cancer.

Keywords: Antiviral Immune Response; Human Leukocyte Antigen; Immunity; Regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Hepacivirus / physiology*
  • Hepatitis C / drug therapy
  • Histocompatibility Antigens Class I / physiology*
  • Humans
  • Killer Cells, Natural / immunology*
  • Lymphocyte Activation*
  • Receptors, KIR3DS1 / physiology*
  • Virus Replication*

Substances

  • HLA-F antigens
  • Histocompatibility Antigens Class I
  • KIR3DS1 protein, human
  • Receptors, KIR3DS1