Human antibodies that neutralize HIV-1: identification, structures, and B cell ontogenies.
Human antibodies that neutralize HIV-1: identification, structures, and B cell ontogenies.
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DOI：
10.1016/j.immuni.2012.08.012
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发表时间：
2012-09-21
期刊：
影响因子：
32.4
通讯作者：
Mascola JR
中科院分区：
文献类型：
--
作者：
Kwong PD;Mascola JR
约 20% 的 HIV-1 感染者体内会产生中和不同 HIV-1 毒株的抗体，这些抗体的分离和结构表征揭示了它们如何识别包膜糖蛋白刺突。广泛反应性中和抗体仅利用少数尖峰脆弱性位点并集中于选定的识别模式。这些抗体具有不寻常的特征：异常长的互补决定环、广泛的体细胞突变，或两者兼而有之。抗体基因转录本深度测序的最新进展提供了中和抗体发育的遗传记录。这些记录有助于了解原始 B 细胞库、体细胞突变以及由此产生的抗体特征，这些特征对于有效中和 HIV-1 至关重要；在此基础上，我们提出了一种基于个体发育和结构的抗体分类系统。人体免疫系统能够产生广泛中和 HIV-1 的抗体，并且关于如何产生针对 HIV-1 的有效免疫力的观点正在不断积累。
Antibodies that neutralize diverse strains of HIV-1 develop in ~20% of HIV-1-infected individuals, and isolation and structural characterization of these antibodies is revealing how they recognize the envelope glycoprotein spike. Broadly reactive neutralizing antibodies utilize just a few sites of spike vulnerability and converge on select modes of recognition. These antibodies have unusual features: uncommonly long complementarity-determining loops, extensive somatic mutation, or both. Recent advances in deep sequencing of antibody-gene transcripts are providing genetic records of the development of neutralizing antibodies. These records inform an understanding of the naïve B cell repertoire, of somatic mutation, and of the resulting antibody features that are critical to effective HIV-1 neutralization; based on these, we propose an ontogeny and structure-based system of antibody classification. The human immune system is capable of developing antibodies that broadly neutralize HIV-1 – and an increasingly detailed view is accumulating for how effective immunity against HIV-1 can be generated.