Antigenic conservation and immunogenicity of the HIV coreceptor binding site.
Antigenic conservation and immunogenicity of the HIV coreceptor binding site.
复制标题
DOI：
10.1084/jem.20042510
复制
发表时间：
2005-05-02
期刊：
影响因子：
--
通讯作者：
Shaw GM
中科院分区：
文献类型：
--
作者：
Decker JM;Bibollet-Ruche F;Wei X;Wang S;Levy DN;Wang W;Delaporte E;Peeters M;Derdeyn CA;Allen S;Hunter E;Saag MS;Hoxie JA;Hahn BH;Kwong PD;Robinson JE;Shaw GM
HIV-1包膜糖蛋白的免疫原性、广泛反应性表位可以作为自然感染中适应性体液免疫应答的重要靶点，并可能作为获得性免疫缺陷综合征疫苗的组成部分。然而，暴露的表位的可变性和高效的病毒掩蔽策略的组合使得这些表位的鉴定成问题。在这里，我们表明，从进化枝A，B，C，D，F，G，和H和循环重组形式（CRF）01，CRF 02，和CRF 11的HIV-1的趋化因子辅助受体结合位点，激发高滴度的CD 4诱导（CD 4 i）抗体在自然人感染，这些抗体结合和中和病毒的分歧作为HIV-2在可溶性CD 4（sCD 4）的存在。189例HIV-1感染患者中有178例（94%）具有中和sCD 4预处理的HIV-2的CD 4 i抗体，滴度（50%抑制浓度）高达1：143，000。由HIV-1感染引起的CD 4 i单克隆抗体也中和用sCD 4预处理的HIV-2，并且来自HIV-1感染者的多克隆抗体特异性地与这样的单克隆抗体竞争结合。在体内，在人血浆中检测到具有自发暴露的辅助受体结合表面的HIV-1变体;这些病毒被CD 4 i抗体直接中和。尽管灵长类慢病毒之间存在显着的进化多样性，但对受体结合的功能限制为广泛的体液免疫识别创造了机会，这反过来又限制了病毒准种。
Immunogenic, broadly reactive epitopes of the HIV-1 envelope glycoprotein could serve as important targets of the adaptive humoral immune response in natural infection and, potentially, as components of an acquired immune deficiency syndrome vaccine. However, variability in exposed epitopes and a combination of highly effective envelope-cloaking strategies have made the identification of such epitopes problematic. Here, we show that the chemokine coreceptor binding site of HIV-1 from clade A, B, C, D, F, G, and H and circulating recombinant form (CRF)01, CRF02, and CRF11, elicits high titers of CD4-induced (CD4i) antibody during natural human infection and that these antibodies bind and neutralize viruses as divergent as HIV-2 in the presence of soluble CD4 (sCD4). 178 out of 189 (94%) HIV-1–infected patients had CD4i antibodies that neutralized sCD4-pretreated HIV-2 in titers (50% inhibitory concentration) as high as 1:143,000. CD4i monoclonal antibodies elicited by HIV-1 infection also neutralized HIV-2 pretreated with sCD4, and polyclonal antibodies from HIV-1–infected humans competed specifically with such monoclonal antibodies for binding. In vivo, variants of HIV-1 with spontaneously exposed coreceptor binding surfaces were detected in human plasma; these viruses were neutralized directly by CD4i antibodies. Despite remarkable evolutionary diversity among primate lentiviruses, functional constraints on receptor binding create opportunities for broad humoral immune recognition, which in turn serves to constrain the viral quasispecies.