Influence of KIR gene copy number on natural killer cell education

Blood. 2013 Jun 6;121(23):4703-7. doi: 10.1182/blood-2012-10-461442. Epub 2013 May 1.

Abstract

Natural killer (NK) cells are functionally tuned by education via killer cell immunoglobulin receptors (KIRs) interacting with HLA class I molecules. We examined the effect of KIR gene copy number variation on the education of human NK cells. The frequency of NK cells expressing a given KIR correlated with the copy number of that gene. However, coexpression of multiple copies from a single locus, or duplicated loci, was infrequent, which is in line with independent transcriptional regulation of each allele or copy. Intriguingly, coexpression of 2 KIR alleles, resulting in higher surface expression, did not lead to enhanced functional responses in vitro or to selective advantages during in vivo responses to cytomegalovirus infection, suggesting that receptor density does not influence NK education at the single cell level. However, individuals with multiple KIR gene copies had higher frequencies of responding cells, consistent with heightened overall responsiveness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cytomegalovirus / immunology
  • Cytomegalovirus Infections / immunology
  • Cytomegalovirus Infections / pathology
  • Cytomegalovirus Infections / virology
  • DNA Copy Number Variations / genetics*
  • Flow Cytometry
  • Gene Expression Regulation
  • Genotype
  • HLA Antigens / metabolism*
  • Humans
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / virology
  • Lysosomal-Associated Membrane Protein 1 / metabolism*
  • Middle Aged
  • NK Cell Lectin-Like Receptor Subfamily C / metabolism*
  • Polymerase Chain Reaction
  • Receptors, KIR / genetics*
  • Receptors, KIR / metabolism
  • Young Adult

Substances

  • HLA Antigens
  • KLRC2 protein, human
  • Lysosomal-Associated Membrane Protein 1
  • NK Cell Lectin-Like Receptor Subfamily C
  • Receptors, KIR