抗体依赖性、FcγRI 介导的 TZM-bl 细胞中 HIV-1 的中和作用不依赖于吞噬作用。
Antibody-DEPENDENT, FcγRI-mediated neutralization of HIV-1 in TZM-bl cells occurs independently of phagocytosis.
机构信息
Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA.
出版信息
J Virol. 2013 May;87(9):5287-90. doi: 10.1128/JVI.00278-13. Epub 2013 Feb 13.
Abstract
We previously showed that expression of human FcγRI on TZM-bl cells potentiates neutralization by gp41 membrane-proximal external region (MPER)-specific antibodies. Here we show that lysosomotropic reagents known to block phagocytosis do not diminish this effect. We also show that FcγRI occasionally potentiates neutralization by antibodies against the V3 loop of gp120 and cluster I of gp41. We conclude that FcγRI provides a kinetic advantage for neutralizing antibodies against partially cryptic epitopes independent of phagocytosis.
摘要
我们之前曾表明，在 TZM-bl 细胞上表达人 FcγRI 可增强 gp41 膜近端外区域（MPER）特异性抗体的中和作用。在这里，我们表明，已知可阻断吞噬作用的溶酶体趋化性试剂不会减弱这种作用。我们还表明，FcγRI 偶尔会增强针对 gp120 的 V3 环和 gp41 簇 I 的抗体的中和作用。我们的结论是，FcγRI 为针对部分隐匿表位的中和抗体提供了一种独立于吞噬作用的动力学优势。
相似文献
1
Antibody-DEPENDENT, FcγRI-mediated neutralization of HIV-1 in TZM-bl cells occurs independently of phagocytosis.抗体依赖性、FcγRI 介导的 TZM-bl 细胞中 HIV-1 的中和作用不依赖于吞噬作用。
J Virol. 2013 May;87(9):5287-90. doi: 10.1128/JVI.00278-13. Epub 2013 Feb 13.
2
Utilization of immunoglobulin G Fc receptors by human immunodeficiency virus type 1: a specific role for antibodies against the membrane-proximal external region of gp41.1型人类免疫缺陷病毒对免疫球蛋白G Fc受体的利用：针对gp41膜近端外部区域抗体的特定作用。
J Virol. 2009 Aug;83(15):7397-410. doi: 10.1128/JVI.00656-09. Epub 2009 May 20.
3
Anti-V3/Glycan and Anti-MPER Neutralizing Antibodies, but Not Anti-V2/Glycan Site Antibodies, Are Strongly Associated with Greater Anti-HIV-1 Neutralization Breadth and Potency.抗V3/聚糖和抗膜近端外部区域（MPER）中和抗体，而非抗V2/聚糖位点抗体，与更强的抗HIV-1中和广度和效力密切相关。
J Virol. 2015 May;89(10):5264-75. doi: 10.1128/JVI.00129-15. Epub 2015 Feb 11.
4
The high-affinity immunoglobulin receptor FcγRI potentiates HIV-1 neutralization via antibodies against the gp41 N-heptad repeat.高亲和力免疫球蛋白受体 FcγRI 通过针对 gp41 N-七肽重复序列的抗体增强 HIV-1 中和作用。
Proc Natl Acad Sci U S A. 2021 Jan 19;118(3). doi: 10.1073/pnas.2018027118.
5
HIV type 1 Env precursor cleavage state affects recognition by both neutralizing and nonneutralizing gp41 antibodies.1型人类免疫缺陷病毒包膜前体的切割状态影响中和性和非中和性gp41抗体的识别。
AIDS Res Hum Retroviruses. 2011 Aug;27(8):877-87. doi: 10.1089/AID.2010.0281. Epub 2011 Jan 19.
6
Increased Epitope Complexity Correlated with Antibody Affinity Maturation and a Novel Binding Mode Revealed by Structures of Rabbit Antibodies against the Third Variable Loop (V3) of HIV-1 gp120.兔抗 HIV-1 gp120 第三可变环（V3）区抗体结构揭示抗原表位复杂度增加与抗体亲和力成熟及新结合模式的相关性。
J Virol. 2018 Mar 14;92(7). doi: 10.1128/JVI.01894-17. Print 2018 Apr 1.
7
Enhancing HIV-1 Neutralization by Increasing the Local Concentration of Membrane-Proximal External Region-Directed Broadly Neutralizing Antibodies.通过增加膜近端外部区域导向的广谱中和抗体的局部浓度来增强 HIV-1 中和作用。
J Virol. 2023 Jan 31;97(1):e0164722. doi: 10.1128/jvi.01647-22. Epub 2022 Dec 21.
8
Conformational Epitope-Specific Broadly Neutralizing Plasma Antibodies Obtained from an HIV-1 Clade C-Infected Elite Neutralizer Mediate Autologous Virus Escape through Mutations in the V1 Loop.从一名感染HIV-1 C亚型的精英中和者体内获得的构象表位特异性广泛中和性血浆抗体通过V1环区的突变介导自体病毒逃逸。
J Virol. 2016 Jan 13;90(7):3446-57. doi: 10.1128/JVI.03090-15.
9
Production and characterization of human anti-V3 monoclonal antibodies from the cells of HIV-1 infected Indian donors.从感染 HIV-1 的印度供体的细胞中生产和鉴定人抗 V3 单克隆抗体。
Virol J. 2012 Sep 12;9:196. doi: 10.1186/1743-422X-9-196.
10
Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity.HIV-1 gp41 膜近端区的氨基酸变化控制病毒中和敏感性。
EBioMedicine. 2016 Oct;12:196-207. doi: 10.1016/j.ebiom.2016.08.045. Epub 2016 Aug 31.
引用本文的文献
1
A broad antibody with enhanced HIV-1 neutralization via bispecific antibody-mediated prepositioning.一种通过双特异性抗体介导的预定位作用具有增强的HIV-1中和能力的广谱抗体。
Nat Commun. 2025 May 18;16(1):4617. doi: 10.1038/s41467-025-60035-6.
2
Isolation and characterization of IgG3 glycan-targeting antibodies with exceptional cross-reactivity for diverse viral families.分离和鉴定对多种病毒家族具有异常交叉反应性的 IgG3 聚糖靶向抗体。
PLoS Pathog. 2024 Sep 18;20(9):e1012499. doi: 10.1371/journal.ppat.1012499. eCollection 2024 Sep.
3
HIV-1 prehairpin intermediate inhibitors show efficacy independent of neutralization tier.HIV-1 发夹前中间体抑制剂的疗效不依赖中和作用。
Proc Natl Acad Sci U S A. 2023 Feb 21;120(8):e2215792120. doi: 10.1073/pnas.2215792120. Epub 2023 Feb 16.
4
Enhancing HIV-1 Neutralization by Increasing the Local Concentration of Membrane-Proximal External Region-Directed Broadly Neutralizing Antibodies.通过增加膜近端外部区域导向的广谱中和抗体的局部浓度来增强 HIV-1 中和作用。
J Virol. 2023 Jan 31;97(1):e0164722. doi: 10.1128/jvi.01647-22. Epub 2022 Dec 21.
5
A Holistic Review of the Preclinical Landscape for Long-Acting Anti-infective Drugs Using HIV as a Paradigm.以 HIV 为例对长效抗感染药物的临床前研究现状进行全面回顾。
Clin Infect Dis. 2022 Nov 21;75(Suppl 4):S490-S497. doi: 10.1093/cid/ciac685.
6
Antibody-drug conjugates with dual payloads for combating breast tumor heterogeneity and drug resistance.具有双重有效载荷的抗体药物偶联物，用于对抗乳腺肿瘤异质性和耐药性。
Nat Commun. 2021 Jun 10;12(1):3528. doi: 10.1038/s41467-021-23793-7.
7
A Derivative of the D5 Monoclonal Antibody That Targets the gp41 N-Heptad Repeat of HIV-1 with Broad Tier-2-Neutralizing Activity.一种针对 HIV-1 gp41 N-七肽重复序列的 D5 单克隆抗体衍生物，具有广泛的 Tier-2 中和活性。
J Virol. 2021 Jul 12;95(15):e0235020. doi: 10.1128/JVI.02350-20.
8
A new lease on life for an HIV-neutralizing antibody class and vaccine target.一类HIV中和抗体及疫苗靶点迎来了新的生机。
Proc Natl Acad Sci U S A. 2021 Feb 16;118(7). doi: 10.1073/pnas.2026390118.
9
The high-affinity immunoglobulin receptor FcγRI potentiates HIV-1 neutralization via antibodies against the gp41 N-heptad repeat.高亲和力免疫球蛋白受体 FcγRI 通过针对 gp41 N-七肽重复序列的抗体增强 HIV-1 中和作用。
Proc Natl Acad Sci U S A. 2021 Jan 19;118(3). doi: 10.1073/pnas.2018027118.
10
Neutralizing Antibodies Targeting HIV-1 gp41.靶向 HIV-1 gp41 的中和抗体。
Viruses. 2020 Oct 23;12(11):1210. doi: 10.3390/v12111210.
本文引用的文献
1
Functional and immunochemical cross-reactivity of V2-specific monoclonal antibodies from HIV-1-infected individuals.HIV-1 感染者来源的 V2 特异性单克隆抗体的功能和免疫化学交叉反应性。
Virology. 2012 Jun 5;427(2):198-207. doi: 10.1016/j.virol.2012.02.003. Epub 2012 Mar 7.
2
Isolation of a human anti-HIV gp41 membrane proximal region neutralizing antibody by antigen-specific single B cell sorting.抗原特异性单个 B 细胞分选分离人抗 HIV gp41 膜近端区中和抗体。
PLoS One. 2011;6(9):e23532. doi: 10.1371/journal.pone.0023532. Epub 2011 Sep 30.
3
Cross-reactive HIV-1-neutralizing human monoclonal antibodies identified from a patient with 2F5-like antibodies.从一位具有 2F5 样抗体的患者中鉴定出的交叉反应性 HIV-1 中和人源单克隆抗体。
J Virol. 2011 Nov;85(21):11401-8. doi: 10.1128/JVI.05312-11. Epub 2011 Aug 31.
4
A robust, high-throughput assay to determine the phagocytic activity of clinical antibody samples.一种用于测定临床抗体样本吞噬活性的稳健、高通量检测方法。
J Immunol Methods. 2011 Mar 7;366(1-2):8-19. doi: 10.1016/j.jim.2010.12.016. Epub 2010 Dec 27.
5
Coordination of Fc receptor signaling regulates cellular commitment to phagocytosis.Fc 受体信号的协调调节细胞对吞噬作用的定向。
Proc Natl Acad Sci U S A. 2010 Nov 9;107(45):19332-7. doi: 10.1073/pnas.1008248107. Epub 2010 Oct 25.
6
Replication competent molecular clones of HIV-1 expressing Renilla luciferase facilitate the analysis of antibody inhibition in PBMC.复制型 HIV-1 分子克隆表达海肾荧光素酶，有助于分析 PBMC 中的抗体抑制作用。
Virology. 2010 Dec 5;408(1):1-13. doi: 10.1016/j.virol.2010.08.028. Epub 2010 Sep 21.
7
Broadly neutralizing monoclonal antibodies 2F5 and 4E10 directed against the human immunodeficiency virus type 1 gp41 membrane-proximal external region protect against mucosal challenge by simian-human immunodeficiency virus SHIVBa-L.广谱中和单克隆抗体 2F5 和 4E10 针对人类免疫缺陷病毒 1 型 gp41 膜近端外部区域，可预防猴免疫缺陷病毒 SHIVBa-L 的粘膜攻击。
J Virol. 2010 Feb;84(3):1302-13. doi: 10.1128/JVI.01272-09. Epub 2009 Nov 11.
8
The CDK inhibitor p21Cip1/WAF1 is induced by FcgammaR activation and restricts the replication of human immunodeficiency virus type 1 and related primate lentiviruses in human macrophages.细胞周期蛋白依赖性激酶（CDK）抑制剂p21Cip1/WAF1由Fcγ受体激活诱导产生，并限制人类免疫缺陷病毒1型及相关灵长类慢病毒在人类巨噬细胞中的复制。
J Virol. 2009 Dec;83(23):12253-65. doi: 10.1128/JVI.01395-09. Epub 2009 Sep 16.
9
Utilization of immunoglobulin G Fc receptors by human immunodeficiency virus type 1: a specific role for antibodies against the membrane-proximal external region of gp41.1型人类免疫缺陷病毒对免疫球蛋白G Fc受体的利用：针对gp41膜近端外部区域抗体的特定作用。
J Virol. 2009 Aug;83(15):7397-410. doi: 10.1128/JVI.00656-09. Epub 2009 May 20.
10
Receptor-mediated phagocytosis elicits cross-presentation in nonprofessional antigen-presenting cells.受体介导的吞噬作用可在非专职抗原呈递细胞中引发交叉呈递。
Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3324-9. doi: 10.1073/pnas.0813305106. Epub 2009 Feb 13.
Zotero 插件