Liyen Loh, Philippa M. Saunders, Camilla Faoro, Neus Font-Porterias, Neda Nemat-Gorgani, Genelle F. Harrison, Suraju Sadeeq, Luca Hensen, Shu Cheng Wong, Jacqueline Widjaja, E. Bridie Clemens, Shiying Zhu, Katherine M. Kichula, Sudan Tao, Faming Zhu, Gonzalo Montero-Martin, Marcelo Fernandez-Vina, Lisbeth A. Guethlein, Julian P. Vivian, Jane Davies, Paul J. Norman
{"title":"An archaic HLA class I receptor allele diversifies natural killer cell-driven immunity in First Nations peoples of Oceania","authors":"Liyen Loh, Philippa M. Saunders, Camilla Faoro, Neus Font-Porterias, Neda Nemat-Gorgani, Genelle F. Harrison, Suraju Sadeeq, Luca Hensen, Shu Cheng Wong, Jacqueline Widjaja, E. Bridie Clemens, Shiying Zhu, Katherine M. Kichula, Sudan Tao, Faming Zhu, Gonzalo Montero-Martin, Marcelo Fernandez-Vina, Lisbeth A. Guethlein, Julian P. Vivian, Jane Davies, Paul J. Norman","doi":"10.1016/j.cell.2024.10.005","DOIUrl":null,"url":null,"abstract":"Genetic variation in host immunity impacts the disproportionate burden of infectious diseases that can be experienced by First Nations peoples. Polymorphic human leukocyte antigen (HLA) class I and killer cell immunoglobulin-like receptors (KIRs) are key regulators of natural killer (NK) cells, which mediate early infection control. How this variation impacts their responses across populations is unclear. We show that HLA-A<sup>∗</sup>24:02 became the dominant ligand for inhibitory KIR3DL1 in First Nations peoples across Oceania, through positive natural selection. We identify KIR3DL1<sup>∗</sup>114, widespread across and unique to Oceania, as an allele lineage derived from archaic humans. KIR3DL1<sup>∗</sup>114<sup>+</sup>NK cells from First Nations Australian donors are inhibited through binding HLA-A<sup>∗</sup>24:02. The KIR3DL1<sup>∗</sup>114 lineage is defined by phenylalanine at residue 166. Structural and binding studies show phenylalanine 166 forms multiple unique contacts with HLA-peptide complexes, increasing both affinity and specificity. Accordingly, assessing immunogenetic variation and the functional implications for immunity are fundamental toward understanding population-based disease associations.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":"103 1","pages":""},"PeriodicalIF":5.7000,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Chemical Theory and Computation","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.cell.2024.10.005","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}
引用次数: 0
Abstract
Genetic variation in host immunity impacts the disproportionate burden of infectious diseases that can be experienced by First Nations peoples. Polymorphic human leukocyte antigen (HLA) class I and killer cell immunoglobulin-like receptors (KIRs) are key regulators of natural killer (NK) cells, which mediate early infection control. How this variation impacts their responses across populations is unclear. We show that HLA-A∗24:02 became the dominant ligand for inhibitory KIR3DL1 in First Nations peoples across Oceania, through positive natural selection. We identify KIR3DL1∗114, widespread across and unique to Oceania, as an allele lineage derived from archaic humans. KIR3DL1∗114+NK cells from First Nations Australian donors are inhibited through binding HLA-A∗24:02. The KIR3DL1∗114 lineage is defined by phenylalanine at residue 166. Structural and binding studies show phenylalanine 166 forms multiple unique contacts with HLA-peptide complexes, increasing both affinity and specificity. Accordingly, assessing immunogenetic variation and the functional implications for immunity are fundamental toward understanding population-based disease associations.
期刊介绍:
The Journal of Chemical Theory and Computation invites new and original contributions with the understanding that, if accepted, they will not be published elsewhere. Papers reporting new theories, methodology, and/or important applications in quantum electronic structure, molecular dynamics, and statistical mechanics are appropriate for submission to this Journal. Specific topics include advances in or applications of ab initio quantum mechanics, density functional theory, design and properties of new materials, surface science, Monte Carlo simulations, solvation models, QM/MM calculations, biomolecular structure prediction, and molecular dynamics in the broadest sense including gas-phase dynamics, ab initio dynamics, biomolecular dynamics, and protein folding. The Journal does not consider papers that are straightforward applications of known methods including DFT and molecular dynamics. The Journal favors submissions that include advances in theory or methodology with applications to compelling problems.