ArticlePLoS genetics2015
Loss and Gain of Natural Killer Cell Receptor Function in an African Hunter-Gatherer Population.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 49 citations in OpenAlex.
- Molecular characterization of the archaic HLA-B∗73:01 allele reveals presentation of a unique peptidome and skewed engagement by KIR2DL2.The Journal of biological chemistry · 2025Article
- Article
- Allelic variation of KIR and HLA tunes the cytolytic payload and determines functional hierarchy of NK cell repertoires.Blood advances · 2023Article
- Epitope characterization of a monoclonal antibody that selectively recognizes KIR2DL1 allotypes.HLA · 2022Article
- Characterization of KIRHLA · 2022Article
- Immunogenomics of Killer Cell Immunoglobulin-Like Receptor (KIR) and HLA Class I: Coevolution and Consequences for Human Health.The journal of allergy and clinical immunology. In practice · 2022Article
- Host KIR/HLA-C Genotypes Determine HIV-Mediated Changes of the NK Cell Repertoire and Are Associated With Vpu Sequence Variations Impacting Downmodulation of HLA-C.Frontiers in immunology · 2022Article
- Liver mesenchymal stem cells are superior inhibitors of NK cell functions through differences in their secretome compared to other mesenchymal stem cells.Frontiers in immunology · 2022Article
- The New Kid on the Block: HLA-C, a Key Regulator of Natural Killer Cells in Viral Immunity.Cells · 2021Review
- Following Transplantation for Acute Myelogenous Leukemia, DonorJournal of immunology (Baltimore, Md. : 1950) · 2021Article
- Adaptive Admixture of HLA Class I Allotypes Enhanced Genetically Determined Strength of Natural Killer Cells in East Asians.Molecular biology and evolution · 2021Article
- Structural plasticity of KIR2DL2 and KIR2DL3 enables altered docking geometries atop HLA-C.Nature communications · 2021Article
- Article
- Tuning of human NK cells by endogenous HLA-C expression.Immunogenetics · 2020Review
- Single Nucleotide Polymorphism inFrontiers in immunology · 2020Article
- The Genetic Mechanisms Driving Diversification of theFrontiers in immunology · 2020Review
- Human NK cell receptor KIR2DS4 detects a conserved bacterial epitope presented by HLA-C.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Diversity of KIR, HLA Class I, and Their Interactions in Seven Populations of Sub-Saharan Africans.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Killer Ig-Like Receptors (KIRs): Their Role in NK Cell Modulation and Developments Leading to Their Clinical Exploitation.Frontiers in immunology · 2019Review
- Two to Tango: Co-evolution of Hominid Natural Killer Cell Receptors and MHC.Frontiers in immunology · 2019Review
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Modulating natural killer cell functions in human immunity and reproduction are diverse interactions between the killer cell immunoglobulin-like receptors (KIR) of Natural Killer (NK) cells and HLA class I ligands on the surface of tissue cells. Dominant interactions are between KIR2DL1 and the C2 epitope of HLA-C and between KIR2DL2/3 and the C1 epitope of HLA-C. KhoeSan hunter-gatherers of Southern Africa represent the earliest population divergence known and are the most genetically diverse indigenous people, qualities reflected in their KIR and HLA genes. Of the ten KhoeSan KIR2DL1 alleles, KIR2DL1*022 and KIR2DL1*026 likely originated in the KhoeSan, and later were transmitted at low frequency to the neighboring Zulus through gene flow. These alleles arose by point mutation from other KhoeSan KIR2DL1 alleles that are more widespread globally. Mutation of KIR2DL1*001 gave rise to KIR2DL1*022, causing loss of C2 recognition and gain of C1 recognition. This makes KIR2DL1*022 a more avid and specific C1 receptor than any KIR2DL2/3 allotype. Mutation of KIR2DL1*012 gave rise to KIR2DL1*026, causing premature termination of translation at the end of the transmembrane domain. This makes KIR2DL1*026 a membrane-associated receptor that lacks both a cytoplasmic tail and signaling function. At higher frequencies than their parental allotypes, the combined effect of the KhoeSan-specific KIR2DL1*022 and KIR2DL1*026 is to reduce the frequency of strong inhibitory C2 receptors and increase the frequency of strong inhibitory C1 receptors. Because interaction of KIR2DL1 with C2 is associated with risk of pregnancy disorder, these functional changes are potentially advantageous. Whereas all other KhoeSan KIR2DL1 alleles are present on a wide diversity of centromeric KIR haplotypes, KIR2DL1*026 is present on a single KIR haplotype and KIR2DL1*022 is present on two very similar haplotypes. The high linkage disequilibrium across their haplotypes is consistent with a recent emergence for these KIR2DL1 alleles that have distinctive functions.
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