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NK cell functions are modulated by interactions between polymorphic inhibitory killer cell immunoglobulin-like receptors (KIR) and polymorphic HLA-A, -B, and -C ligands expressed on tissue cells. All HLA-C alleles encode a KIR ligand and contribute to reproduction and immunity. In contrast, only some HLA-A and -B alleles encode KIR ligands and they focus on immunity. By high-resolution analysis of KIR and HLA-A, -B, and -C genes, we show that the Chinese Southern Han (CHS) are significantly enriched for interactions between inhibitory KIR and HLA-A and -B. This enrichment has had substantial input through population admixture with neighboring populations, who contributed HLA class I haplotypes expressing the KIR ligands B*46:01 and B*58:01, which subsequently rose to high frequency by natural selection. Consequently, over 80% of Southern Han HLA haplotypes encode more than one KIR ligand. Complementing the high number of KIR ligands, the CHS KIR locus combines a high frequency of genes expressing potent inhibitory KIR, with a low frequency of those expressing activating KIR. The Southern Han centromeric KIR region encodes strong, conserved, inhibitory HLA-C-specific receptors, and the telomeric region provides a high number and diversity of inhibitory HLA-A and -B-specific receptors. In all these characteristics, the CHS represent other East Asians, whose NK cell repertoires are thus enhanced in quantity, diversity, and effector strength, likely augmenting resistance to endemic viral infections.<\/jats:p>","DOI":"10.1093\/molbev\/msab053","type":"journal-article","created":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T01:06:43Z","timestamp":1613610403000},"page":"2582-2596","source":"Crossref","is-referenced-by-count":29,"title":["Adaptive Admixture of HLA Class I Allotypes Enhanced Genetically Determined Strength of Natural Killer Cells in East Asians"],"prefix":"10.1093","volume":"38","author":[{"given":"Zhihui","family":"Deng","sequence":"first","affiliation":[{"name":"Immunogenetics Laboratory, Shenzhen Blood Center , Shenzhen, Guangdong, P. R. China"},{"name":"Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University , Guangzhou, Guangdong, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxin","family":"Zhen","sequence":"additional","affiliation":[{"name":"Immunogenetics Laboratory, Shenzhen Blood Center , Shenzhen, Guangdong, P. R. China"},{"name":"Central Laboratory, Shenzhen Baoan Women\u2019s and Children\u2019s Hospital , Shenzhen, Guangdong, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genelle F","family":"Harrison","sequence":"additional","affiliation":[{"name":"Division of Biomedical Informatics and Personalized Medicine, University of Colorado, Anschutz Medical Campus , Aurora, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guobin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Immunogenetics Laboratory, Shenzhen Blood Center , Shenzhen, Guangdong, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Chen","sequence":"additional","affiliation":[{"name":"Immunogenetics Laboratory, Shenzhen Blood Center , Shenzhen, Guangdong, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Sun","sequence":"additional","affiliation":[{"name":"Immunogenetics Laboratory, Shenzhen Blood Center , Shenzhen, Guangdong, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Yu","sequence":"additional","affiliation":[{"name":"Immunogenetics Laboratory, Shenzhen Blood Center , Shenzhen, Guangdong, P. R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojiang","family":"Gao","sequence":"additional","affiliation":[{"name":"Inflammatory Cell Dynamics Section, Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, NIH , Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqi","family":"Cai","sequence":"additional","affiliation":[{"name":"Immunogenetics Laboratory, Shenzhen Blood Center , Shenzhen, Guangdong, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William H","family":"Palmer","sequence":"additional","affiliation":[{"name":"Division of Biomedical Informatics and Personalized Medicine, University of Colorado, Anschutz Medical Campus , Aurora, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan A","family":"Shortt","sequence":"additional","affiliation":[{"name":"Division of Biomedical Informatics and Personalized Medicine, University of Colorado, Anschutz Medical Campus , Aurora, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher R","family":"Gignoux","sequence":"additional","affiliation":[{"name":"Division of Biomedical Informatics and Personalized Medicine, University of Colorado, Anschutz Medical Campus , Aurora, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Carrington","sequence":"additional","affiliation":[{"name":"Basic Science Program, Frederick National Laboratory for Cancer Research (FNLCR), Frederick, MD21702, and Ragon Institute of MGH , Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Zou","sequence":"additional","affiliation":[{"name":"Immunogenetics Laboratory, Shenzhen Blood Center , Shenzhen, Guangdong, P. 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