Killer cell immunoglobulin-like receptor 3DL1 licenses CD16-mediated effector functions of natural killer cells

J Leukoc Biol. 2010 Nov;88(5):905-12. doi: 10.1189/jlb.1009687. Epub 2010 Jul 27.


Activating receptor-mediated recognition of stress-induced ligands or IgG antibody bridging of tumor or pathogen-associated antigens to the FcγRIII CD16 triggers NK cells to kill transformed and infected cells with reduced HLA-I expression. According to the licensing hypothesis, NK cells become competent for activating receptor-mediated triggering after a formative encounter between a NK inhibitory receptor and its ligand. This general hypothesis is supported by murine and human studies, but to date, evidence of a role for such licensing in human ADCC is ambiguous. Inhibitory receptor interactions with HLA-C promote NK cell ADCC licensing, but interactions between KIR3DL1 and its HLA-Bw4 ligand may be insufficient. We investigated the impact of KIR3DL1 and HLA-Bw4 coexpression on NK cell ADCC using a robust, genuine target system of antibody-bearing EBV-transformed B lymphocytes. Although numbers of KIR3DL1(+) NK cells were similar in HLA-Bw4(+) and HLA-Bw4(-) individuals, general levels of ADCC mediated against target cells were significantly higher in a group of HLA-Bw4(+)KIR3DL1(+) individuals than in a comparable HLA-Bw4(-) group. Flow cytometry demonstrated directly that a significantly higher fraction of KIR3DL1(+) NK cells derived from HLA-Bw4(+) compared with HLA-Bw4(-) individuals produced IFN-γ following stimulation with ADCC targets. Murine FcR-bearing P815 target cells also triggered higher levels of CD16-mediated cytotoxicity by NK cells from HLA-Bw4(+)KIR3DL1(+) individuals. These results indicate a prominent role for KIR3DL1/HLA-Bw4 interactions in licensing NK cells for CD16-mediated effector function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Inflammation / immunology
  • Inflammation / physiopathology
  • Killer Cells, Natural / immunology*
  • Mutation
  • Niemann-Pick Diseases / enzymology
  • Niemann-Pick Diseases / genetics
  • Pain / immunology
  • Pain / physiopathology
  • Receptors, IgG / immunology*
  • Receptors, KIR3DL1 / immunology*
  • Sphingomyelin Phosphodiesterase / genetics


  • Receptors, IgG
  • Receptors, KIR3DL1
  • SMPD1 protein, human
  • Sphingomyelin Phosphodiesterase