Oboshi Wataru, Watanabe Toru, Matsuyama Yuumi, Kobara Ayana, Yukimasa Nobuyasu, Ueno Ichiro, Aki Kensaku, Tada Tomoki, Hosoi Eiji
Department of Medical Technology, Kagawa Prefectural University of Health Sciences, 281-1 Hara, Mure-cho, Takamatsu, Kagawa 761-0123, Japan; Subdivision of Biomedical Laboratory Sciences, Graduate School of Health Sciences, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima 770-8509, Japan.
The Graduate School of Health Sciences, Kagawa Prefectural University of Health Sciences, 281-1 Hara, Mure-cho, Takamatsu, Kagawa 761-0123, Japan.
Hum Immunol. 2016 Feb;77(2):165-71. doi: 10.1016/j.humimm.2015.11.001. Epub 2015 Nov 12.
NK cells express the CD16 (FcγRIIIa) receptor, which mediates antibody-dependent cellular cytotoxicity (ADCC), on their cell surface. Therefore, ADCC activity may be influenced by qualitative or quantitative changes in the CD16 molecule on NK cells. Responses to NK cell-mediated ADCC have been shown to depend on single nucleotide polymorphisms (SNPs) at FcγRIIIa amino acid position 158. However, a consensus has not yet been reached regarding differences in the structure and expression levels of the CD16 molecule among FcγRIIIa-V158F genotypes, which have not yet been adequately investigated in healthy Japanese individuals. We herein examined the influence of the FcγRIIIa polymorphism on ADCC, binding affinity of CD16 to the Fc region, FCGR3A gene expression, and cell-surface CD16 expression in healthy Japanese subjects. FcγRIIIa-V158F genotyping was performed for 101 subjects. The results obtained showed that all parameters analyzed increased in the order of V/V>V/F>F/F and were significantly higher in V/V subjects than in F/F subjects. Moreover, a positive correlation was observed between ADCC activity and binding affinity, FCGR3A transcript levels, and surface CD16 expression levels. These results suggest that the structure and expression of the CD16 molecule differs among FcγRIIIa-V158F genotypes, and the FcγRIIIa-V158F polymorphism may be represent a haplotype with other SNPs in regulatory regions in Japanese subjects.
自然杀伤（NK）细胞在其细胞表面表达CD16（FcγRIIIa）受体，该受体介导抗体依赖性细胞毒性（ADCC）。因此，ADCC活性可能会受到NK细胞上CD16分子的定性或定量变化的影响。已证明对NK细胞介导的ADCC的反应取决于FcγRIIIa氨基酸位置158处的单核苷酸多态性（SNP）。然而，关于FcγRIIIa - V158F基因型之间CD16分子的结构和表达水平差异尚未达成共识，在健康日本个体中尚未对此进行充分研究。我们在此研究了FcγRIIIa多态性对健康日本受试者的ADCC、CD16与Fc区域的结合亲和力、FCGR3A基因表达以及细胞表面CD16表达的影响。对101名受试者进行了FcγRIIIa - V158F基因分型。所得结果表明，所有分析参数按V/V>V/F>F/F的顺序增加，且V/V受试者中的参数显著高于F/F受试者。此外，观察到ADCC活性与结合亲和力、FCGR3A转录水平和表面CD16表达水平之间存在正相关。这些结果表明，CD16分子的结构和表达在FcγRIIIa - V158F基因型之间存在差异，并且FcγRIIIa - V158F多态性可能代表日本受试者中与调控区域其他SNP的单倍型。
