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Primary Human Neutrophils Exhibit a Unique HIV-Directed Antibody-Dependent Phagocytosis Profile.
Journal of Innate Immunity ( IF 4.7 ) Pub Date : 2018-12-17 , DOI: 10.1159/000494371
Rebecca L R Powell 1 , Alisa Fox 2 , Vincenza Itri 2 , Susan Zolla-Pazner 2
Affiliation  

The only clinical HIV vaccine trial to demonstrate efficacy, RV144, correlated protection with the antibodies (Abs) mediating function via the "constant" immunoglobulin region, the crystallizable fragment (Fc). These data have supported a focus on the induction of Abs by vaccines that trigger antiviral activities by relevant leukocytes via Fc receptors (FcRs). Neutrophils are phagocytes that comprise > 50% of leukocytes and display unique FcRs. We sought to compare the Ab-dependent cellular phagocytosis (ADCP) activity of human neutrophils to the commonly assayed THP-1 cell line. HIV-specific Abs were employed to elicit ADCP of beads coated with HIV envelope protein. Overall, trends were noted among neutrophil donors and the ADCP profile was different from that of THP-1 cells. mAb ELISA titers correlated with ADCP by THP-1 cells but not neutrophils. Monoclonal (m)Abs were also tested with primary monocytes. Donor-to-donor variation was high, and hindered the analysis of this dataset, but it was, in itself, an important finding. This study illustrates the concept that the assessment of FcR-mediated Ab activity with a frequently used cell line such as THP-1 is not necessarily indicative of relevant Ab functionality in vivo, and this calls for in-depth study of the properties of the HIV antibodies best-suited to eliciting antiviral activities by primary cells.

中文翻译:

初级人类嗜中性粒细胞表现出独特的HIV导向的抗体依赖性吞噬作用概况。

唯一证明功效的临床HIV疫苗试验RV144通过“恒定”免疫球蛋白区域(可结晶片段(Fc))将保护与抗体​​(Abs)介导的功能相关联。这些数据支持着重于通过相关受体白细胞经由Fc受体(FcR)触发抗病毒活性的疫苗诱导抗体的研究。中性粒细胞是吞噬细胞,占白细胞的50%以上,并显示独特的FcR。我们试图将人类嗜中性粒细胞的Ab依赖性细胞吞噬作用(ADCP)活性与通常测定的THP-1细胞系进行比较。HIV特异性抗体被用来引发涂有HIV包膜蛋白的微珠的ADCP。总体而言,在中性粒细胞供体之间注意到了趋势,并且ADCP谱不同于THP-1细胞。通过THP-1细胞,mAb ELISA滴度与ADCP相关,但与中性粒细胞无关。还用原代单核细胞测试了单克隆(m)Ab。供体之间的差异很大,阻碍了该数据集的分析,但这本身就是一个重要发现。这项研究阐明了这样一个概念,即使用常用的细胞系(例如THP-1)评估FcR介导的Ab活性不一定表明体内相关的Ab功能,这需要对HIV特性进行深入研究。最适合通过原代细胞引发抗病毒活性的抗体。
更新日期:2019-11-01
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