Influence of KIR gene copy number on natural killer cell education

• Published in: Blood 2013-06, Vol.121 (23), p.4703-4707
• Main Authors: Béziat, Vivien, Traherne, James A., Liu, Lisa L., Jayaraman, Jyothi, Enqvist, Monika, Larsson, Stella, Trowsdale, John, Malmberg, Karl-Johan
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Brief Report; 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; Immunobiology; Killer Cells, Natural - cytology; Killer Cells, Natural - immunology; Killer Cells, Natural - virology; Lysosomal-Associated Membrane Protein 1 - metabolism; Medicin och hälsovetenskap; Middle Aged; NK Cell Lectin-Like Receptor Subfamily C - metabolism; Polymerase Chain Reaction; Receptors, KIR - genetics; Receptors, KIR - metabolism; Young Adult
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2012-10-461442

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. •KIR gene copy number variation influences NK cell education at the repertoire level due to a linear effect on KIR expression.•No effect of KIR gene dose on NK cell education at the single cell level.