HLA alleles determine differences in human natural killer cell responsiveness and potency Journal Article


Authors: Kim, S.; Sunwoo, J. B.; Yang, L.; Choi, T.; Song, Y. J.; French, A. R.; Vlahiotis, A.; Piccirillo, J. F.; Cella, M.; Colonna, M.; Mohanakumar, T.; Hsu, K. C.; Dupont, B.; Yokoyama, W. M.
Article Title: HLA alleles determine differences in human natural killer cell responsiveness and potency
Abstract: Epidemiological studies have associated certain human disease outcomes with particular killer cell Ig-like receptor (KIR) and HLA genotypes. However, the functional explanation for these associations is poorly understood, because the KIRs were initially described as natural killer (NK) cell inhibitory receptors with specificity for HLA molecules on their cellular targets. Yet resolution of infections is often associated with genotypic pairing of inhibitory KIRs with their cognate HLA ligands. Recent studies in mice indicate a second role for MHC-specific inhibitory receptors, i.e., self-MHC recognition confers functional competence on the NK cell to be triggered through their activation receptors, a process termed licensing. As a result, licensed NK cells with self-MHC-specific receptors are more readily activated as compared with unlicensed NK cells without self-MHC-specific receptors. Such results predict that human NK cells may undergo a similar process. Here, we examined the human NK cell subset expressing KIR3DL1, the only known KIR specific for HLA-Bw4 alleles. The KIR3DL1+ subset in normal donors with two HLA-B-Bw4 genes displayed increased responsiveness to tumor stimulation compared with the KIR3DL1 + subset from individuals with only one or no Bw4 genes. By contrast, NK cells lacking KIR3DL1 showed no differences. Therefore, these data indicate that particular KIR and HLA alleles are associated with more responsive NK cells, strongly suggesting that human NK cells are also subjected to NK cell licensing, and providing a potential functional explanation for the influence of KIR and HLA genes in disease as well as interindividual differences in NK cell potency. © 2008 by The National Academy of Sciences of the USA.
Keywords: human cell; genetics; comparative study; antigen expression; metabolism; mus; cell function; genotype; cell line, tumor; cytokine; blood; immunology; cytokines; cellular immunity; tumor cell line; cell subpopulation; natural killer cell; killer cells, natural; innate immunity; hla b antigen; licensing; polymorphism, genetic; statistics, nonparametric; hla-b antigens; normal human; genetic polymorphism; hla system; cytotoxicity tests, immunologic; nonparametric test; cytotoxicity test; nk cells; killer cell ig-like receptor (kir); kir3dl1 antigen; hla bw4; hla-bw4; killer cell immunoglobulin like receptor 3dl1; kir3dl1 protein, human; receptors, kir3dl1
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 105
Issue: 8
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2008-02-26
Start Page: 3053
End Page: 3058
Language: English
DOI: 10.1073/pnas.0712229105
PUBMED: 18287063
PROVIDER: scopus
PMCID: PMC2268583
DOI/URL:
Notes: --- - "Cited By (since 1996): 60" - "Export Date: 17 November 2011" - "CODEN: PNASA" - "Source: Scopus"
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MSK Authors
  1. Katharine C Hsu
    149 Hsu
  2. Bo Dupont
    197 Dupont