Signature biochemical properties of broadly cross-reactive HIV-1 neutralizing antibodies in human plasma.
Signature biochemical properties of broadly cross-reactive HIV-1 neutralizing antibodies in human plasma.
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人血浆中广泛交叉反应的 HIV-1 中和抗体的特征生化特性。
DOI：
10.1128/jvi.06547-11
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发表时间：
2012
影响因子：
5.4
通讯作者：
DeVico,AnthonyL
中科院分区：
文献类型：
--
作者：
Sajadi,MohammadM;Lewis,GeorgeK;Seaman,MichaelS;Guan,Yongjun;Redfield,RobertR;DeVico,AnthonyL
在某些HIV-1感染者中发现的广泛交叉反应性HIV-1中和抗体的共同特性对于理解天然和疫苗介导的抗HIV免疫具有重要价值。最近的努力已经解决了这个问题，从选定的受试者的记忆B细胞池中获得中和单克隆抗包膜抗体。然而，更难确定血浆中循环的广泛中和抗体是否具有个体之间的共同特征。为了解决这个问题，我们使用亲和层析和等电聚焦从10名HIV-1感染者（5名具有广泛HIV-1中和活性的受试者和5名对照）中分离血浆免疫球蛋白。我们发现，血浆中和活性通常分为至少两个抗体亚组。具有有限中和宽度的抗体具有相对中性的等电点，并且相对于可变环和其他结构域已被删除的核心抗原，优先结合包膜单体和三聚体。相比之下，广泛中和抗体占总抗包膜应答的一小部分。它们一致地通过更基本的等电点和对单体gp 120、gp 120核心或CD 4诱导结构共享的表位的特异性来区分。这种生物化学特性可能被用来可靠地预测或产生广泛的抗HIV免疫力。
The common properties of broadly cross-reactive HIV-1 neutralization antibodies found in certain HIV-1-infected individuals holds significant value for understanding natural and vaccine-mediated anti-HIV immunity. Recent efforts have addressed this question by deriving neutralizing monoclonal anti-envelope antibodies from memory B cell pools of selected subjects. However, it has been more difficult to identify whether broadly neutralizing antibodies circulating in plasma possess shared characteristics among individuals. To address this question, we used affinity chromatography and isoelectric focusing to fractionate plasma immunoglobulin from 10 HIV-1-infected subjects (5 subjects with broad HIV-1 neutralizing activity and 5 controls). We find that plasma neutralizing activity typically partitions into at least two subsets of antibodies. Antibodies with restricted neutralization breadth have relatively neutral isoelectric points and preferentially bind to envelope monomers and trimers versus core antigens from which variable loops and other domains have been deleted. In comparison, broadly neutralizing antibodies account for a minor fraction of the total anti-envelope response. They are consistently distinguished by more basic isoelectric points and specificity for epitopes shared by monomeric gp120, gp120 core, or CD4-induced structures. Such biochemical properties might be exploited to reliably predict or produce broad anti-HIV immunity.