Fc gamma RIIIa-158V/F polymorphism influences the binding of IgG by natural killer cell Fc gamma RIIIa, independently of the Fc gamma IIIa-48L/R/H phenotype
Fc gamma RIIIa-158V/F polymorphism influences the binding of IgG by natural killer cell Fc gamma RIIIa, independently of the Fc gamma IIIa-48L/R/H phenotype
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DOI：
10.1182/blood.v90.3.1109.1109_1109_1114
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发表时间：
1997-08-01
期刊：
影响因子：
20.3
通讯作者：
deHaas, M
中科院分区：
文献类型：
--
作者：
Koene, HR;Kleijer, M;deHaas, M
我们分析了 Fc γ 受体 IIIa (CD16) 的遗传多态性，该受体位于近膜 IgG 结合域的 158 位（Phe 或 Val）。通过基于聚合酶链反应的等位基因特异性限制性分析测定，我们对 87 名供体进行了基因分型，发现 Fc gamma RIIIA-158F 和 -158V 的基因频率分别为 0.57 和 0.43。一方面FcγRIIIA-158F和-48L基因型与另一方面FcγRIIIA-158V和-48H或-48R基因型之间观察到明显的连锁(chi(2)检验；P<0.001)。为了确定这种 Fc gamma RIIIa-158V/F 多态性的功能后果，我们对来自基因分型供体的自然杀伤 (NK) 细胞进行了 IgG 结合实验。所有供体还针对最近描述的三基因 Fc gamma RIIIa-48L/R/H 多态性进行了分型。用乳酸处理 NK 细胞以去除细胞相关的 IgG。无论 Fc γ RIIIa-48 表型如何，Fc γ RIIIa(NK)-158F 比 Fc γ RIIIa(NK)-158V 结合显着更少的 IgG1、IgG3 和 IgG4。此外，来自 Fc γ RIIIa-158VV 个体的新鲜分离的 NK 细胞比来自 Fc γ RIIIa-158FF 个体的 NK 细胞携带显着更多的亲细胞 IgG。此外，与-158F相比，CD16单克隆抗体(MoAb) MEM154与Fc γ RIIIa-158V的结合更强烈，同样与Fc γ RIIIa-48表型无关。MoAb B73.1的结合不受Fc γ RIIIa-158V/F多态性的影响，但证明仅依赖于Fc γ的位置48处存在的氨基酸。 RIIIa。总之，先前报道的三种 Fc γ RIIIa-48L/R/H 亚型之间 IgG 结合的差异是氨基酸位置 158 处相连的双等位基因 Fc γ RIIIa-158V/F 多态性的结果。(C) 1997，美国血液学会。
We analyzed a genetic polymorphism of Fc gamma receptor IIIa (CD16) that is present on position 158 (Phe or Val) in the membrane-proximal, IgG-binding domain. With a polymerase chain reaction-based allele-specific restriction analysis assay we genotyped 87 donors and found gene frequencies of 0.57 and 0.43 for Fc gamma RIIIA-158F and -158V, respectively. A clear linkage was observed between the Fc gamma RIIIA-158F and -48L genotypes on the one hand and the Fc gamma RIIIA-158V and -48H or -48R genotypes on the other hand (chi(2) test; P < .001). To determine the functional consequences of this Fc gamma RIIIa-158V/F polymorphism, we performed IgG binding experiments with natural killer (NK) cells from genotyped donors, All donors were also typed for the recently described triallelic Fc gamma RIIIa-48L/R/H polymorphism. NK cells were treated with lactic acid to remove cell-associated IgG. Fc gamma RIIIa(NK)-158F bound significantly less IgG1, IgG3, and IgG4 than did Fc gamma RIIIa(NK)-158V, irrespective of the Fc gamma RIIIa-48 phenotype, Moreover, freshly isolated NK cells from Fc gamma RIIIa-158VV individuals carried significantly more cytophilic IgG than did NK cells from Fc gamma RIIIa-158FF individuals. In addition, CD16 monoclonal antibody (MoAb) MEM154 bound more strongly to Fc gamma RIIIa-158V, compared with -158F, again independently of the Fc gamma RIIIa-48 phenotype, The binding of MoAb B73.1 was not influenced by the Fc gamma RIIIa-158V/F polymorphism, but proved to depend solely on the amino acid present at position 48 of Fc gamma RIIIa. In conclusion, the previously reported differences in IgG binding among the three Fc gamma RIIIa-48L/R/H isoforms are a consequence of the linked, biallelic Fc gamma RIIIa-158V/F polymorphism at amino-acid position 158. (C) 1997 by The American Society of Hematology.