Duke University Medical Center, Department of Surgery, P.O. Box 2926, Durham, NC 27710, USA.
J Virol. 2011 Jul;85(14):7029-36. doi: 10.1128/JVI.00171-11. Epub 2011 May 4.
Among nonneutralizing HIV-1 envelope antibodies (Abs), those capable of mediating antibody-dependent cellular cytotoxicity (ADCC) activity have been postulated to be important for control of HIV-1 infection. ADCC-mediating Ab must recognize HIV-1 antigens expressed on the membrane of infected cells and bind the Fcγ receptor (FcR) of the effector cell population. However, the precise targets of serum ADCC antibody are poorly characterized. The human monoclonal antibody (MAb) A32 is a nonneutralizing antibody isolated from an HIV-1 chronically infected person. We investigated the ability of MAb A32 to recognize HIV-1 envelope expressed on the surface of CD4(+) T cells infected with primary and laboratory-adapted strains of HIV-1, as well as its ability to mediate ADCC activity. The MAb A32 epitope was expressed on the surface of HIV-1-infected CD4(+) T cells earlier than the CD4-inducible (CD4i) epitope bound by MAb 17b and the gp120 carbohydrate epitope bound by MAb 2G12. Importantly, MAb A32 was a potent mediator of ADCC activity. Finally, an A32 Fab fragment blocked the majority of ADCC-mediating Ab activity in plasma of subjects chronically infected with HIV-1. These data demonstrate that the epitope defined by MAb A32 is a major target on gp120 for plasma ADCC activity.
在非中和性 HIV-1 包膜抗体（Abs）中，能够介导抗体依赖性细胞毒性（ADCC）活性的抗体被认为对控制 HIV-1 感染很重要。ADCC 介导的 Ab 必须识别感染细胞表面表达的 HIV-1 抗原，并结合效应细胞群体的 Fcγ 受体（FcR）。然而，血清 ADCC 抗体的精确靶标特征描述较差。人源单克隆抗体（MAb）A32 是从 HIV-1 慢性感染者中分离出来的非中和性抗体。我们研究了 MAb A32 识别感染原发性和实验室适应的 HIV-1 株的 CD4(+) T 细胞表面表达的 HIV-1 包膜的能力，以及其介导 ADCC 活性的能力。MAb A32 表位在 HIV-1 感染的 CD4(+) T 细胞表面的表达时间早于 MAb 17b 结合的 CD4 诱导（CD4i）表位和 MAb 2G12 结合的 gp120 碳水化合物表位。重要的是，MAb A32 是 ADCC 活性的有效介质。最后，A32 Fab 片段阻断了慢性 HIV-1 感染受试者血浆中大多数 ADCC 介导 Ab 活性。这些数据表明，MAb A32 定义的表位是 gp120 上用于血浆 ADCC 活性的主要靶标。
