Effects of NKG2D haplotypes on the cell-surface expression of NKG2D protein on natural killer and CD8 T cells of peripheral blood among atomic-bomb survivors
Effects of NKG2D haplotypes on the cell-surface expression of NKG2D protein on natural killer and CD8 T cells of peripheral blood among atomic-bomb survivors
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DOI：
10.1016/j.humimm.2012.03.003
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发表时间：
2012-06-01
期刊：
影响因子：
2.7
通讯作者：
Nakachi, Kei
中科院分区：
文献类型：
--
作者：
Imai, Kazue;Hayashi, Tomonori;Nakachi, Kei
NKG 2D是一种主要活化受体，可触发NK细胞中细胞介导的细胞毒性，对抗肿瘤和病毒感染的细胞。我们先前在染色体12 p上的自然杀伤基因复合体区域中鉴定了NKG 2D单倍型。两个主要的单倍型等位基因，LNK 1和HNK 1，分别与低和高的天然细胞毒活性表型密切相关。此外，HNK 1/HNK 1的单倍型显示与LNK 1/LNK 1相比癌症风险降低。在本研究中，使用流式细胞术，我们评估了NKG 2D单倍型和5个htSNPs的功能影响的NKG 2D蛋白的细胞表面表达的NK和CD 8 T细胞的外周血732原子弹爆炸幸存者。NK细胞上的NKG 2D表达显示出显著增加，按LNK 1/LNK 1、LNK 1/HNK 1和HNK 1/HNK 1单倍型的顺序（趋势p = 0.003），或单个htSNP的主要纯合、杂合和次要纯合基因型（趋势p = 0.02-0.003）。在CD 8 T细胞上观察到NKG 2D表达的相同趋势。我们的研究结果表明，NKG 2D单倍型与NK和CD 8 T细胞上NKG 2D蛋白的表达水平相关，导致人类细胞毒性反应的个体间差异。(C)2012年美国组织相容性和免疫遗传学学会。爱思唯尔公司出版All rights reserved.
NKG2D is a primary activating receptor that triggers cell-mediated cytotoxicity in NK cells against tumor and virus-infected cells. We previously identified the NKG2D haplotypes in the natural killer gene complex region on chromosome 12p. Two major haplotype alleles, LNK1 and HNK1, were closely related to low and high natural cytotoxic activity phenotypes, respectively. Furthermore, the haplotype of HNK1/HNK1 has revealed a decreased risk of cancer compared with LNK1/LNK1. In the present study, using flow cytometry, we evaluated the functional effects of NKG2D haplotypes and five htSNPs in terms of the cell-surface expression of NKG2D protein on NK and CD8 T cells of peripheral blood among 732 atomic-bomb survivors. NKG2D expression on NK cells showed significant increases, in the order of LNK1/LNK1, LNK1/HNK1 and HNK1/HNK1 haplotypes (p for trend = 0.003), or with major homozygous, heterozygous, and minor homozygous genotypes for individual htSNPs (p for trend = 0.02-0.003). The same trend was observed for NKG2D expression on CD8 T cells. Our findings indicate that the NKG2D haplotypes are associated with the expression levels of NKG2D protein on NK and CD8 T cells, resulting in inter-individual variations in human cytotoxic response. (C) 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.