KIR2DL2 enhances protective and detrimental HLA class I-mediated immunity in chronic viral infection

PLoS Pathog. 2011 Oct;7(10):e1002270. doi: 10.1371/journal.ppat.1002270. Epub 2011 Oct 13.

Abstract

Killer cell immunoglobulin-like receptors (KIRs) influence both innate and adaptive immunity. But while the role of KIRs in NK-mediated innate immunity is well-documented, the impact of KIRs on the T cell response in human disease is not known. Here we test the hypothesis that an individual's KIR genotype affects the efficiency of their HLA class I-mediated antiviral immune response and the outcome of viral infection. We show that, in two unrelated viral infections, hepatitis C virus and human T lymphotropic virus type 1, possession of the KIR2DL2 gene enhanced both protective and detrimental HLA class I-restricted anti-viral immunity. These results reveal a novel role for inhibitory KIRs. We conclude that inhibitory KIRs, in synergy with T cells, are a major determinant of the outcome of persistent viral infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Female
  • Genes, MHC Class I
  • HTLV-I Infections / genetics
  • HTLV-I Infections / immunology*
  • HTLV-I Infections / virology
  • Hepacivirus / immunology
  • Hepacivirus / physiology
  • Hepatitis C, Chronic / genetics
  • Hepatitis C, Chronic / immunology*
  • Hepatitis C, Chronic / virology
  • Histocompatibility Antigens Class I / immunology*
  • Human T-lymphotropic virus 1 / immunology
  • Human T-lymphotropic virus 1 / physiology
  • Humans
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Killer Cells, Natural / virology
  • Male
  • Receptors, KIR / immunology
  • Receptors, KIR2DL2 / genetics*
  • Receptors, KIR2DL2 / metabolism*
  • T-Lymphocytes / immunology
  • Viral Load

Substances

  • Histocompatibility Antigens Class I
  • KIR2DL2 protein, human
  • Receptors, KIR
  • Receptors, KIR2DL2