Misra Maneesh K, Augusto Danillo G, Martin Gonzalo Montero, Nemat-Gorgani Neda, Sauter Jürgen, Hofmann Jan A, Traherne James A, González-Quezada Betsy, Gorodezky Clara, Bultitude Will P, Marin Wesley, Vierra-Green Cynthia, Anderson Kirsten M, Balas Antonio, Caro-Oleas Jose L, Cisneros Elisa, Colucci Francesco, Dandekar Ravi, Elfishawi Sally M, Fernández-Viña Marcelo A, Fouda Merhan, González-Fernández Rafael, Große Arend, Herrero-Mata Maria J, Hollenbach Sam Q, Marsh Steven G E, Mentzer Alex, Middleton Derek, Moffett Ashley, Moreno-Hidalgo Miguel A, Mossallam Ghada I, Nakimuli Annettee, Oksenberg Jorge R, Oppenheimer Stephen J, Parham Peter, Petzl-Erler Maria-Luiza, Planelles Dolores, Sánchez-García Florentino, Sánchez-Gordo Francisco, Schmidt Alexander H, Trowsdale John, Vargas Luciana B, Vicario Jose L, Vilches Carlos, Norman Paul J, Hollenbach Jill A
Department of Neurology, University of California San Francisco, San Francisco, CA 94158, USA.
Department of Neurology, University of California San Francisco, San Francisco, CA 94158, USA; Department of Genetics, Universidade Federal do Paraná, Curitiba, Brazil.
Hum Immunol. 2018 Dec;79(12):825-833. doi: 10.1016/j.humimm.2018.10.003. Epub 2018 Oct 12.
The goals of the KIR component of the 17th International HLA and Immunogenetics Workshop (IHIW) were to encourage and educate researchers to begin analyzing KIR at allelic resolution, and to survey the nature and extent of KIR allelic diversity across human populations. To represent worldwide diversity, we analyzed 1269 individuals from ten populations, focusing on the most polymorphic KIR genes, which express receptors having three immunoglobulin (Ig)-like domains (KIR3DL1/S1, KIR3DL2 and KIR3DL3). We identified 13 novel alleles of KIR3DL1/S1, 13 of KIR3DL2 and 18 of KIR3DL3. Previously identified alleles, corresponding to 33 alleles of KIR3DL1/S1, 38 of KIR3DL2, and 43 of KIR3DL3, represented over 90% of the observed allele frequencies for these genes. In total we observed 37 KIR3DL1/S1 allotypes, 40 for KIR3DL2 and 44 for KIR3DL3. As KIR allotype diversity can affect NK cell function, this demonstrates potential for high functional diversity worldwide. Allelic variation further diversifies KIR haplotypes. We determined KIR3DL3 ∼ KIR3DL1/S1 ∼ KIR3DL2 haplotypes from five of the studied populations, and observed multiple population-specific haplotypes in each. This included 234 distinct haplotypes in European Americans, 191 in Ugandans, 35 in Papuans, 95 in Egyptians and 86 in Spanish populations. For another 35 populations, encompassing 642,105 individuals we focused on KIR3DL2 and identified another 375 novel alleles, with approximately half of them observed in more than one individual. The KIR allelic level data gathered from this project represents the most comprehensive summary of global KIR allelic diversity to date, and continued analysis will improve understanding of KIR allelic polymorphism in global populations. Further, the wealth of new data gathered in the course of this workshop component highlights the value of collaborative, community-based efforts in immunogenetics research, exemplified by the IHIW.
第17届国际HLA与免疫遗传学研讨会(IHIW)的杀伤细胞免疫球蛋白样受体(KIR)部分的目标是鼓励并指导研究人员开始以等位基因分辨率分析KIR,并调查全球人群中KIR等位基因多样性的性质和程度。为了体现全球多样性,我们分析了来自十个群体的1269名个体,重点关注多态性最高的KIR基因,这些基因表达具有三个免疫球蛋白(Ig)样结构域的受体(KIR3DL1/S1、KIR3DL2和KIR3DL3)。我们鉴定出KIR3DL1/S1的13个新等位基因、KIR3DL2的13个新等位基因以及KIR3DL3的18个新等位基因。先前鉴定的等位基因,对应于KIR3DL1/S1的33个等位基因、KIR3DL2的38个等位基因以及KIR3DL3的43个等位基因,占这些基因观察到的等位基因频率的90%以上。我们总共观察到37种KIR3DL1/S1别型、40种KIR3DL2别型和44种KIR3DL3别型。由于KIR别型多样性会影响自然杀伤(NK)细胞功能,这表明全球存在高功能多样性的潜力。等位基因变异进一步使KIR单倍型多样化。我们确定了来自五个研究群体的KIR3DL3∼KIR3DL1/S1∼KIR3DL2单倍型,并在每个群体中观察到多种特定于群体的单倍型。这包括欧裔美国人中的234种不同单倍型、乌干达人中的191种、巴布亚人中的35种、埃及人中的95种以及西班牙人群体中的86种。对于另外35个群体,涵盖642,105名个体,我们重点关注KIR3DL2并鉴定出另外375个新等位基因,其中约一半在不止一个个体中被观察到。从该项目收集的KIR等位基因水平数据代表了迄今为止全球KIR等位基因多样性最全面的总结,持续分析将增进对全球人群中KIR等位基因多态性的理解。此外,在本次研讨会部分过程中收集的大量新数据凸显了免疫遗传学研究中基于社区的合作努力的价值,以IHIW为例。