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N332 定向广谱中和抗体采用多种 HIV-1 识别模式:从重链-轻链功能互补推断。

N332-Directed broadly neutralizing antibodies use diverse modes of HIV-1 recognition: inferences from heavy-light chain complementation of function.

机构信息

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.

出版信息

PLoS One. 2013;8(2):e55701. doi: 10.1371/journal.pone.0055701. Epub 2013 Feb 19.

Abstract

Dozens of broadly neutralizing HIV-1 antibodies have been isolated in the last few years from the sera of HIV-1-infected individuals. Only a limited number of regions on the HIV-1 spike, however, are recognized by these antibodies. One of these regions (N332) is characterized by an N-linked glycan at residue 332 on HIV-1 gp120 and is recognized by antibody 2G12 and by the recently reported antibodies PGT121-137, the latter isolated from three donors. To investigate the diversity in mode of antibody recognition at the N332 site, we used functional complementation between antibody heavy and light chains as a means of assessing similarity in mode of recognition. We examined a matrix of 12 PGT-heavy chains with each of 12 PGT-light chains. Expression in 96-well format for the 144 antibodies (132 chimeric and 12 wild-type) was generally consistent (58 ± 10 µg/ml). In contrast, recognition of HIV-1 gp120 was bimodal: when the source of heavy and light chains was from the same donor, recognition was good; when sources of heavy and light chains were from different donors, recognition was poor. Moreover, neutralization of HIV-1 strains SF162.LS and TRO.11 generally followed patterns of gp120 recognition. These results are consistent with published sequence, mutational, and structural findings, all of which indicate that N332-directed neutralizing antibodies from different donors utilize different modes of recognition, and provide support for a correlation between functional complementation of antibody heavy and light chains and similarity in antibody mode of recognition. Overall, our results add to the growing body of evidence that the human immune system is capable of recognizing the N332-region of HIV-1 gp120 in diverse ways.

摘要

在过去的几年中,已经从 HIV-1 感染个体的血清中分离出了数十种广谱中和 HIV-1 的抗体。然而,这些抗体只能识别 HIV-1 刺突上的有限数量的区域。其中一个区域(N332)位于 HIV-1 gp120 上的第 332 位残基的 N 连接糖基化上,由抗体 2G12 和最近报道的 PGT121-137 抗体识别,后者从三个供体中分离得到。为了研究在 N332 位点上抗体识别模式的多样性,我们使用抗体重链和轻链之间的功能互补作为评估识别模式相似性的一种手段。我们用 12 种 PGT 重链和 12 种 PGT 轻链组成了一个矩阵进行研究。对于这 144 种抗体(132 种嵌合抗体和 12 种野生型抗体)在 96 孔格式中的表达通常是一致的(58 ± 10 µg/ml)。相比之下,HIV-1 gp120 的识别呈双峰模式:当重链和轻链的来源来自同一供体时,识别效果良好;当重链和轻链的来源来自不同供体时,识别效果较差。此外,SF162.LS 和 TRO.11 两种 HIV-1 株的中和作用通常遵循 gp120 识别模式。这些结果与已发表的序列、突变和结构研究结果一致,所有这些结果均表明,来自不同供体的 N332 定向中和抗体利用不同的识别模式,并且支持抗体重链和轻链的功能互补与抗体识别模式的相似性之间存在相关性。总体而言,我们的结果进一步证明,人类免疫系统能够以不同的方式识别 HIV-1 gp120 的 N332 区域。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a5/3576407/bb68abbf86cc/pone.0055701.g001.jpg

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