KIR2DS5 allotypes that recognize the C2 epitope of HLA-C are common among Africans and absent from Europeans.
KIR2DS5 allotypes that recognize the C2 epitope of HLA-C are common among Africans and absent from Europeans.
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DOI：
10.1002/iid3.178
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发表时间：
2017-12
期刊：
影响因子：
--
通讯作者：
Parham P
中科院分区：
文献类型：
--
作者：
Blokhuis JH;Hilton HG;Guethlein LA;Norman PJ;Nemat-Gorgani N;Nakimuli A;Chazara O;Moffett A;Parham P
KIR 2DS 5是谱系III KIR的活化人NK细胞受体。这些包括抑制性KIR 2DL 1、2和3以及识别HLA-C的C1或C2表位的激活性KIR 2DS 1。在欧洲，KIR 2DS 5基本上是单态的，其中KIR 2DS 5 *002占主导地位。开创性研究表明，KIR 2DS 5 *002具有激活潜力，但不能识别HLA-A、-B或-C。随后的研究表明，KIR 2DS 5在非洲人中具有高度多态性，KIR 2DS 5 *006可保护乌干达孕妇免受先兆子痫的影响。由于抑制性C2特异性KIR 2DL 1与先兆子痫相关，而激活C2特异性KIR 2DS 1起保护作用，这种关联表明KIR 2DS 5 *006是激活性C2特异性受体。为了检验这一假设，我们从所有10种KIR 2DS 5同种异型制备了KIR-Fc融合蛋白，并测试了它们与代表性的HLA-A、-B和-C同种异型的结合。6个非洲特异性KIR 2DS 5结合C2+ HLA-C，但不结合其他HLA I类。它们对C2的亲合力是C2特异性KIR 2DL 1的约20%，是C2特异性KIR 2DS 1的约40%。在非洲C2受体中，KIR 2DS 5 *006可以保护一组乌干达孕妇免受先兆子痫的影响。三种非洲KIR 2DS 5同种异型和KIR 2DS 5 *002不结合HLA-A、-B或-C。作为一个组，与非结合KIR 2DS 5同种异型相比，C2结合KIR 2DS 5同种异型保护免于先兆子痫。导致C2受体功能丧失或降低的天然取代位于D2结构域的127、158和176位。 KIR 2DS 5 *005具有KIR 2DS 5共有序列，是在KIR 2DS 5的着丝粒和端粒位置处发现的唯一等位基因，并且可能是所有KIR 2DS 5等位基因的共同祖先。KIR 2DS 5 *005具有C2受体活性，表明KIR 2DS 5 *002和其他缺乏C2受体功能的同种异型是减毒产物，这是大多数KIR B单倍型基因的特征。编码减弱的和活性的KIR 2DS 5的等位基因存在于着丝粒和端粒位置。
KIR2DS5 is an activating human NK cell receptor of lineage III KIR. These include both inhibitory KIR2DL1, 2 and 3 and activating KIR2DS1 that recognize either the C1 or C2 epitope of HLA‐C. In Europeans KIR2DS5 is essentially monomorphic, with KIR2DS5*002 being predominant. Pioneering investigations showed that KIR2DS5*002 has activating potential, but cannot recognize HLA‐A, ‐B, or ‐C. Subsequent studies have shown that KIR2DS5 is highly polymorphic in Africans, and that KIR2DS5*006 protects pregnant Ugandan women from preeclampsia. Because inhibitory C2‐specific KIR2DL1 correlates with preeclampsia, whereas activating C2‐specific KIR2DS1 protects, this association pointed to KIR2DS5*006 being an activating C2‐specific receptor. To test this hypothesis we made KIR‐Fc fusion proteins from all ten KIR2DS5 allotypes and tested their binding to a representative set of HLA‐A, ‐B and ‐C allotypes. Six African‐specific KIR2DS5 bound to C2+HLA‐C but not to other HLA class I. Their avidity for C2 is ∼20% that of C2‐specific KIR2DL1 and ∼40% that of C2‐specific KIR2DS1. Among the African C2 receptors is KIR2DS5*006, which protected a cohort of pregnant Ugandans from pre‐eclampsia. Three African KIR2DS5 allotypes and KIR2DS5*002, bound no HLA‐A, ‐B or ‐C. As a group the C2‐binding KIR2DS5 allotypes protect against pre‐eclampsia compared to the non‐binding KIR2DS5 allotypes. Natural substitutions that contribute to loss or reduction of C2 receptor function are at positions 127, 158, and 176 in the D2 domain. KIR2DS5*005 has the KIR2DS5 consensus sequence, is the only allele found at both centromeric and telomeric locations of KIR2DS5, and is likely the common ancestor of all KIR2DS5 alleles. That KIR2DS5*005 has C2 receptor activity, points to KIR2DS5*002, and other allotypes lacking C2 receptor function, being products of attenuation, a characteristic feature of most KIR B haplotype genes. Alleles encoding attenuated and active KIR2DS5 are present in both centromeric and telomeric locations.
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DOI：
10.4049/jimmunol.1001951
发表时间：
2010-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Moesta AK;Graef T;Abi-Rached L;Older Aguilar AM;Guethlein LA;Parham P
通讯作者：
Parham P
在人类天然杀伤细胞中，HLA-C分子的抑制（p58）和激活（p50）受体的存在。
影响因子：
15.3
作者：
Moretta, Alessandro;Sivori, Simona;Vitale, Massimo;Pende, Daniela;Morelli, Luiga;Augugliaro, Raffaella;Bottino, Cristina;Moretta, Lorenzo
通讯作者：
Moretta, Lorenzo
影响因子：
2.7
作者：
Hou, LiHua;Chen, Minghua;Jiang, Bo;Kariyawasam, Kanthi;Ng, Jennifer;Hurley, Carolyn Katovich
通讯作者：
Hurley, Carolyn Katovich
影响因子：
4.4
作者：
Hilton, Hugo G.;Blokhuis, Jeroen H.;Parham, Peter
通讯作者：
Parham, Peter
DOI：
10.1073/pnas.1413453112
发表时间：
2015-01-20
影响因子：
11.1
作者：
Nakimuli, Annettee;Chazara, Olympe;Moffett, Ashley
通讯作者：
Moffett, Ashley