Boudet F, Girard M, Theze J, Zouali M
Unité d'Immunogénétique Cellulaire, Institut Pasteur, Paris, France.
Int Immunol. 1992 Feb;4(2):283-94. doi: 10.1093/intimm/4.2.283.
Several motifs have been found to be the target of the neutralizing antibody response to HIV, the human immunodeficiency virus. One of the well characterized motifs maps to a loop within the third hypervariable region (V3) of the exterior envelope glycoprotein gp120 at amino acid positions 308-331 and is referred to as the principal neutralizing determinant (PND). The sequence of this V3 loop raises the question of the immunogenicity and the degree of diversity of the antibody response to the PND. We show here that this neutralization-related motif is highly immunogenic in HIV-positive subjects and in experimentally immunized primates and rodents submitted to various anti-HIV immunization regimens. In probing the diversity of the antibody response to PNDs corresponding to 11 HIV sequence-divergent isolates in serum samples of 101 HIV-positive individuals we found that human antibodies exhibit binding affinity to up to nine PND synthetic peptides. This antibody binding was in all cases tested inhibitable by the homologous PND synthetic peptide. We additionally demonstrate that this antibody cross-reactivity towards sequence-divergent PNDs is detectable in the sera of mice and chimpanzees experimentally immunized against a single HIV-1 isolate. Finally, we noticed that there is a hierarchy of reactivity among the various PNDs wherein the synthetic peptide corresponding to the MN isolate was generally the most prominently recognized by antibodies of human, non-human primate, and rodent origins. Based on these findings and on features of the sequences analyzed we suggest that, despite its overall sequence variability, the PND encompasses conserved amino acid positions or epitopes that are the targets of antibodies recognizing sequence-divergent isolates. We also propose that the high positive charge density of the most frequently recognized PNDs and the high antigenicity value of some of their residues are critical to the broad immunoreactivity of this neutralization-related motif.
已发现几种基序是针对人类免疫缺陷病毒（HIV）的中和抗体反应的靶点。其中一个特征明确的基序位于外膜糖蛋白gp120的第三个高变区（V3）内的一个环上，氨基酸位置为308 - 331，被称为主要中和决定簇（PND）。这个V3环的序列引发了关于对PND的抗体反应的免疫原性和多样性程度的问题。我们在此表明，这个与中和相关的基序在HIV阳性个体以及接受各种抗HIV免疫方案的实验性免疫的灵长类动物和啮齿动物中具有高度免疫原性。在探究101名HIV阳性个体血清样本中对应11种HIV序列不同分离株的PND的抗体反应多样性时，我们发现人类抗体对多达9种PND合成肽具有结合亲和力。在所有测试案例中，这种抗体结合均可被同源PND合成肽抑制。我们还证明，在针对单一HIV - 1分离株进行实验性免疫的小鼠和黑猩猩的血清中可检测到这种针对序列不同的PND的抗体交叉反应性。最后，我们注意到各种PND之间存在反应性层次结构，其中对应MN分离株的合成肽通常最容易被人类、非人类灵长类动物和啮齿动物来源的抗体识别。基于这些发现以及所分析序列的特征，我们认为，尽管PND的整体序列具有变异性，但它包含保守的氨基酸位置或表位，这些是识别序列不同分离株的抗体的靶点。我们还提出，最常被识别的PND的高正电荷密度及其一些残基的高抗原性值对于这个与中和相关的基序的广泛免疫反应性至关重要。
