Epitope map of human immunodeficiency virus type 1 gp41 derived from 47 monoclonal antibodies produced by immunization with oligomeric envelope protein
Epitope map of human immunodeficiency virus type 1 gp41 derived from 47 monoclonal antibodies produced by immunization with oligomeric envelope protein
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DOI：
10.1128/jvi.71.4.2674-2684.1997
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发表时间：
1997-04-01
影响因子：
5.4
通讯作者：
Moss, B
中科院分区：
文献类型：
--
作者：
Earl, PL;Broder, CC;Moss, B
人类免疫缺陷病毒1型（HIV-1）包膜（Env）糖蛋白蛋白的生物学相关形式是寡聚的，寡聚伙伴之间的主要接触点位于gp41的外结构域。为了鉴定和定位gp41中结构受四级相互作用影响的保守表位和区域，我们使用了一组38个构象依赖性和9个构象非依赖性的抗gp41单克隆抗体（mab），这些单克隆抗体是由低聚Env蛋白免疫小鼠产生的。通过使用这些单克隆抗体和先前描述的其他几个单克隆抗体进行交叉竞争实验，鉴定并绘制了六个不同的抗原决定因子。其中三个决定因素本质上是构象的，部分依赖于Env寡聚体结构。针对其中两个决定因子的单克隆抗体与源自原代病毒株的Env蛋白具有广泛的交叉反应性。hiv -1阳性的人血清中针对抗原决定因子的抗体的流行程度是由这种血清阻断单克隆抗体与Env蛋白结合的能力决定的。发现强阻断活性与交叉反应性相关。
The biologically relevant form of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein protein is oligomeric, with the major points of contact between oligomeric partners located in the ectodomain of gp41. To identify and map conserved epitopes and regions in gp41 where structure is influenced by quaternary interactions, we used a panel of 38 conformation-dependent and 9 conformation-independent anti-gp41 monoclonal antibodies (MAbs) produced by immunization of mice with oligomeric Env protein. By cross-competition experiments using these MAbs and several others previously described, six distinct antigenic determinants were identified and mapped. Three of these determinants are conformational in nature and dependent in part on Env oligomeric structure. MAbs to two of these determinants were broadly cross-reactive with Env proteins derived from primary virus strains. The prevalence of antibodies in HIV-1-positive human sera to the antigenic determinants was determined by the ability of such sera to block binding of MAbs to Env protein. Strong blocking activity that correlated with cross-reactivity was found.