Co-evolution of KIR2DL3 with HLA-C in a human population retaining minimal essential diversity of KIR and HLA class I ligands
Co-evolution of KIR2DL3 with HLA-C in a human population retaining minimal essential diversity of KIR and HLA class I ligands
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DOI：
10.1073/pnas.0906051106
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发表时间：
2009-11-03
影响因子：
11.1
通讯作者：
Parham, Peter
中科院分区：
文献类型：
--
作者：
Gendzekhadze, Ketevan;Norman, Paul J.;Parham, Peter
自然杀伤（NK）细胞有助于免疫和生殖。指导这些功能和NK细胞教育的是杀伤细胞Ig样受体（KIR），即识别HLA I类的NK细胞受体。在大多数人群中，这些高度多态性的受体和配体联合收割机具有非凡的多样性。为了评估这种多样性的必要性，我们研究了Yucpa的高分辨率KIR和HLA I类，Yucpa是一个小的南美印第安人群体，在大约15，000年的人口瓶颈和流行病感染（包括最近的病毒性肝炎）历史中幸存下来。丝兰保留了KIR识别的三个主要HLA表位。通过对一些不同单倍型的平衡选择，丝兰保留了世界各地发现的大部分KIR变异。HLA-C*07是C1特异性NK细胞的最强教育者，在尤卡帕地区的出现频率非常高。与此同时，C1受体的较弱变体KIR 2DL 3被选中，并在很大程度上取代了来自亚洲的原始移民带来的KIR 2DL 3形式。HLA-C1和KIR 2DL 3的纯合性与对病毒性肝炎的抗性相关。在丝兰中选择较弱形式的KIR 2DL 3可以被视为对高频率的有效HLA-C*07配体的补偿。这项研究提供了一个估计的最小KIR-HLA系统的长期生存所必需的人群。它包含了世界范围内KIR多样性的所有功能要素，证明了它提供的竞争优势，不仅是为了生存流行病感染，而且是为了在感染后重建种群。
Natural killer (NK) cells contribute to immunity and reproduction. Guiding these functions, and NK cell education, are killer cell Ig-like receptors (KIR), NK cell receptors that recognize HLA class I. In most human populations, these highly polymorphic receptors and ligands combine with extraordinary diversity. To assess how much of this diversity is necessary, we studied KIR and HLA class I at high resolution in the Yucpa, a small South Amerindian population that survived an approximate 15,000-year history of population bottleneck and epidemic infection, including recent viral hepatitis. The Yucpa retain the three major HLA epitopes recognized by KIR. Through balancing selection on a few divergent haplotypes the Yucpa maintain much of the KIR variation found worldwide. HLA-C*07, the strongest educator of C1-specific NK cells, has reached unusually high frequency in the Yucpa. Concomitantly, weaker variants of the C1 receptor, KIR2DL3, were selected and have largely replaced the form of KIR2DL3 brought by the original migrants from Asia. HLA-C1 and KIR2DL3 homozygosity has previously been correlated with resistance to viral hepatitis. Selection of weaker forms of KIR2DL3 in the Yucpa can be seen as compensation for the high frequency of the potent HLA-C*07 ligand. This study provides an estimate of the minimal KIR-HLA system essential for long-term survival of a human population. That it contains all functional elements of KIR diversity worldwide, attests to the competitive advantage it provides, not only for surviving epidemic infections, but also for rebuilding populations once infection has passed.