Unusual selection on the KIR3DL1/S1 natural killer cell receptor in Africans
Unusual selection on the KIR3DL1/S1 natural killer cell receptor in Africans
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DOI：
10.1038/ng2111
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发表时间：
2007-09-01
期刊：
影响因子：
30.8
通讯作者：
Parham, Peter
中科院分区：
文献类型：
--
作者：
Norman, Paul J.;Abi-Rached, Laurent;Parham, Peter
杀伤细胞免疫球蛋白样受体 (KIR) 与主要组织相容性复合物 (MHC) I 类配体的相互作用使自然杀伤细胞对感染的反应多样化。通过分析不同人群中的序列变异，我们发现 KIR3DL1/S1 基因座编码两种多态抑制性 KIR3DL1 同种异型谱系，可识别 HLA-A 和 HLA-B 的 Bw4 表位，以及一种保守的激活 KIR3DS1 同种异型谱系，也与 Bw4 识别有关。平衡选择使这三个谱系维持了超过 300 万年。在接触 I 类 HLA 的 D1 和 D2 结构域残基以及增强 KIR3D 与 I 类 HLA 结合的 D0 结构域的两个位点处选择变异。通过等位基因间微转换获得 Bw4 的 HLA-B 变体也是选择的产物。一项全球比较揭示了现代撒哈拉以南非洲人中不寻常的 KIR3DL1/S1 进化。平衡选择较弱且仅限于 D0，KIR3DS1 很少见，并且具有相似结合位点的 KIR3DL1 同种异型占主导地位。自然杀伤细胞以高频率和高表面密度表达占主导地位的 KIR3DL1，为 Bw4 表达受到干扰的细胞提供强烈的反应。
Interactions of killer cell immunoglobulin- like receptors ( KIRs) with major histocompatibility complex ( MHC) class I ligands diversify natural killer cell responses to infection. By analyzing sequence variation in diverse human populations, we show that the KIR3DL1/ S1 locus encodes two lineages of polymorphic inhibitory KIR3DL1 allotypes that recognize Bw4 epitopes of HLA- A and HLA- B and one lineage of conserved activating KIR3DS1 allotypes, also implicated in Bw4 recognition. Balancing selection has maintained these three lineages for over 3 million years. Variation was selected at D1 and D2 domain residues that contact HLA class I and at two sites on D0, the domain that enhances the binding of KIR3D to HLA class I. HLA- B variants that gained Bw4 through interallelic microconversion are also products of selection. A worldwide comparison uncovers unusual KIR3DL1/ S1 evolution in modern sub- Saharan Africans. Balancing selection is weak and confined to D0, KIR3DS1 is rare and KIR3DL1 allotypes with similar binding sites predominate. Natural killer cells express the dominant KIR3DL1 at a high frequency and with high surface density, providing strong responses to cells perturbed in Bw4 expression.