Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1
Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1
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DOI：
10.1038/ng2035
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发表时间：
2007-06-01
期刊：
影响因子：
30.8
通讯作者：
Carrington, Mary
中科院分区：
文献类型：
--
作者：
Martin, Maureen P.;Qi, Ying;Carrington, Mary
自然杀伤（NK）细胞受体KIR 3DL 1的同种异型在NK细胞表达模式和与其存在于靶细胞上的配体HLA-B Bw 4分子结合后的抑制能力方面都不同。使用超过1，500名人类免疫缺陷病毒（HIV）（+）个体的样本量，我们表明KIR 3DL 1和HLA-B基因座的各种不同等位基因组合以一致的方式显著且强烈地影响AIDS进展和血浆HIV RNA丰度。这些遗传数据与先前定义的区分KIR 3DL 1同种异型的功能差异非常相关。这里观察到的常见的、不同的KIR 3DL 1和HLA-B Bw 4组合的各种上位效应对于人类疾病中的任何一对遗传位点都是前所未有的，并且表明NK细胞可能在HIV感染的自然史中具有关键作用。
Allotypes of the natural killer ( NK) cell receptor KIR3DL1 vary in both NK cell expression patterns and inhibitory capacity upon binding to their ligands, HLA-B Bw4 molecules, present on target cells. Using a sample size of over 1,500 human immunodeficiency virus (HIV)(+) individuals, we show that various distinct allelic combinations of the KIR3DL1 and HLA-B loci significantly and strongly influence both AIDS progression and plasma HIV RNA abundance in a consistent manner. These genetic data correlate very well with previously defined functional differences that distinguish KIR3DL1 allotypes. The various epistatic effects observed here for common, distinct KIR3DL1 and HLA-B Bw4 combinations are unprecedented with regard to any pair of genetic loci in human disease, and indicate that NK cells may have a critical role in the natural history of HIV infection.