Montero-Martin Gonzalo, Kichula Katherine M, Misra Maneesh K, de Brito Vargas Luciana, Marin Wesley M, Hollenbach Jill A, Fernández-Viña Marcelo A, Elfishawi Sally, Norman Paul J
Stanford Blood Center, Department of Pathology, Stanford University, Stanford, California, USA.
Department of Biomedical Informatics, University of Colorado School of Medicine, Aurora, Colorado, USA.
HLA. 2024 Jan;103(1):e15177. doi: 10.1111/tan.15177. Epub 2023 Aug 2.
Genetically determined variation of killer cell immunoglobulin like receptors (KIR) and their HLA class I ligands affects multiple aspects of human health. Their extreme diversity is generated through complex interplay of natural selection for pathogen resistance and reproductive health, combined with demographic structure and dispersal. Despite significant importance to multiple health conditions of differential effect across populations, the nature and extent of immunogenetic diversity is under-studied for many geographic regions. Here, we describe the first high-resolution analysis of KIR and HLA class I combinatorial diversity in Northern Africa. Analysis of 125 healthy unrelated individuals from Cairo in Egypt yielded 186 KIR alleles arranged in 146 distinct centromeric and 79 distinct telomeric haplotypes. The most frequent haplotypes observed were KIR-A, encoding two inhibitory receptors specific for HLA-C, two that are specific for HLA-A and -B, and no activating receptors. Together with 141 alleles of HLA class I, 75 of which encode a KIR ligand, we identified a mean of six distinct interacting pairs of inhibitory KIR and HLA allotypes per individual. We additionally characterize 16 KIR alleles newly identified in the study population. Our findings place Egyptians as one of the most highly diverse populations worldwide, with important implications for transplant matching and studies of immune-mediated diseases.
杀伤细胞免疫球蛋白样受体（KIR）及其HLA I类配体的基因决定变异影响人类健康的多个方面。它们的极端多样性是通过对病原体抗性和生殖健康的自然选择与人口结构及扩散的复杂相互作用产生的。尽管对不同人群有不同影响的多种健康状况具有重要意义，但许多地理区域的免疫遗传多样性的性质和程度仍未得到充分研究。在这里，我们描述了北非地区KIR和HLA I类组合多样性的首次高分辨率分析。对来自埃及开罗的125名健康无关个体的分析产生了186个KIR等位基因，这些等位基因排列在146个不同的着丝粒单倍型和79个不同的端粒单倍型中。观察到的最常见单倍型是KIR-A，它编码两种对HLA-C特异的抑制性受体、两种对HLA-A和-B特异的抑制性受体，且没有激活受体。连同141个HLA I类等位基因（其中75个编码KIR配体），我们确定每个个体平均有六对不同的抑制性KIR和HLA同种异型相互作用对。我们还对研究人群中新鉴定的16个KIR等位基因进行了表征。我们的研究结果表明埃及人是世界上免疫遗传多样性最高的人群之一，这对移植配型和免疫介导疾病的研究具有重要意义。
