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Updated: Jul 7, 2026
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qKAT: Quantitative Semi-automated Typing of Killer-cell Immunoglobulin-like Receptor Genes
Published on: March 6, 2019
HLA alleles determine differences in human natural killer cell responsiveness and potency
Sungjin Kim1, John B Sunwoo, Liping Yang
1Howard Hughes Medical Institute, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Summary
Human natural killer (NK) cells expressing killer cell Ig-like receptors (KIR) and HLA-Bw4 alleles show increased tumor responsiveness. This suggests NK cell licensing, explaining KIR-HLA gene influence on disease and NK cell potency.
Area of Science:
- Immunology
- Genetics
Background:
- Killer cell Ig-like receptors (KIR) and HLA genotypes are linked to human disease, but the functional basis is unclear.
- KIRs were thought to only inhibit natural killer (NK) cell activity, but recent mouse studies suggest a role in NK cell licensing.
- NK cell licensing, where self-MHC recognition enhances NK cell responsiveness, is a proposed mechanism.
Purpose of the Study:
- To investigate the functional role of KIR3DL1 and its HLA-Bw4 ligand in human NK cell responsiveness.
- To determine if human NK cells undergo a licensing process similar to that observed in mice.
Main Methods:
- Examined the KIR3DL1(+) NK cell subset in healthy donors.
- Compared NK cell responsiveness to tumor stimulation based on the number of HLA-B-Bw4 genes.
- Analyzed NK cells lacking KIR3DL1 for comparison.
Main Results:
- KIR3DL1(+) NK cells from donors with two HLA-B-Bw4 genes showed enhanced tumor responsiveness.
- KIR3DL1(+) NK cells from donors with one or no Bw4 genes had lower responsiveness.
- NK cells lacking KIR3DL1 did not show significant differences in responsiveness.
Conclusions:
- Specific KIR and HLA alleles are associated with more potent NK cell responses.
- These findings strongly suggest that human NK cells undergo licensing.
- Provides a functional explanation for the impact of KIR and HLA genes on disease susceptibility and NK cell activity.
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