Functional activity of an HIV-1 neutralizing IgG human monoclonal antibody: ADCC and complement-mediated lysis.
Functional activity of an HIV-1 neutralizing IgG human monoclonal antibody: ADCC and complement-mediated lysis.
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HIV-1 中和 IgG 人单克隆抗体的功能活性：ADCC 和补体介导的裂解。
DOI：
10.1089/aid.1992.8.553
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发表时间：
1992
影响因子：
1.5
通讯作者：
Hideshima,T
中科院分区：
文献类型：
--
作者：
Posner,MR;Elboim,HS;Cannon,T;Cavacini,L;Hideshima,T
研究了IgG 1 K（人单克隆抗体（HMAb）F105）在抗体依赖性细胞毒性（ADCC）和补体依赖性细胞毒性（CDC）中的功能活性。F105与表达在感染细胞表面的HIV-1包膜糖蛋白gp 120的CD 4结合位点上的不连续表位反应，并在人体易于达到的抗体浓度下中和不同的病毒株。F105和来自HIV血清阳性供体的血清（1：50稀释）均不介导针对SF 2感染细胞系的CDC，其中兔或人血清作为补体来源。F105和HIV-1血清介导抗SF-2株的ADCC。正常人血清可减少外周血单核细胞对SF 2的自发裂解。尽管F105与正常人血清的混合减少了观察到的溶解（36 ± 8%对42 ± 8%），但这仍然显著大于培养基（30 ± 5%）或正常人血清（23 ± 6%）中的溶解（p <0.05）。抗CD 16的鼠抗体显著降低了用培养基观察到的自发溶解（30 ± 5%对18 ± 3%），而正常小鼠血清没有影响（31 ± 7%）。F105介导的ADCC被抗CD 16抗体完全消除（42 ± 8 vs. 22 ± 4%），而HIV血清介导的ADCC只有一部分被抗CD 16抑制（60 ± 9 vs. 46 ± 6%），这表明多克隆血清介导的ADCC中有几个效应细胞群起作用。因此，与多克隆血清相反，F105通过CD 16 +PBM群体介导ADCC。
The IgG1K, human monoclonal antibody (HMAb), F105, was studied for functional activity in antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). F105 reacts with a discontinuous epitope on the CD4 binding site of the HIV-1 envelope glycoprotein, gp120, expressed on the surfaces of infected cells and neutralizes diverse viral strains at antibody concentrations readily achievable in humans. Neither F105 nor serum (diluted 1:50) from HIV seropositive donors mediate CDC against an SF2-infected cell line with rabbit or human sera as a source of complement. F105 and HIV-1 sera mediate ADCC against the SF2strain. Normal human serum reduced spontaneous lysis of SF2by peripheral blood monocytes (PBM). Although mixing of F105 with normal human serum reduced the lysis observed (36 ± 8 vs. 42 ± 8%), this still was significantly greater than lysis in media (30 ± 5%) or normal human serum (23 ± 6%) (p <.05). A murine antibody to CD16 significantly reduced spontaneous lysis observed with media (30 ± 5 vs. 18 ± 3%) while normal mouse serum had no effect (31 ± 7%). ADCC mediated by F105 is completely abrogated by the anti-CD16 antibody (42 ± 8 vs. 22 ± 4%), while only a fraction of ADCC mediated by HIV sera is inhibited by anti-CD16 (60 ± 9 vs. 46 ± 6%), suggesting that several populations of effector cells function in ADCC mediated by the polyclonal sera. Thus, F105, as opposed to polyclonal sera, mediates ADCC through a CD16+PBM population.