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在一名病毒血症控制者中，广谱 HIV-1 中和 IgA 和 IgG 抗体谱系的表位汇聚。

Epitope convergence of broadly HIV-1 neutralizing IgA and IgG antibody lineages in a viremic controller.

机构信息

Laboratory of Humoral Immunology, Department of Immunology, Institut Pasteur, Paris, France.

Institut national de la santé et de la recherche médicale U1222, Paris, France.

出版信息

J Exp Med. 2022 Mar 7;219(3). doi: 10.1084/jem.20212045. Epub 2022 Mar 1.

DOI:10.1084/jem.20212045
PMID:35230385
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8932546/
Abstract

Decrypting the B cell ontogeny of HIV-1 broadly neutralizing antibodies (bNAbs) is paramount for vaccine design. Here, we characterized IgA and IgG bNAbs of three distinct B cell lineages in a viremic controller, two of which comprised only IgG+ or IgA+ blood memory B cells; the third combined both IgG and IgA clonal variants. 7-269 bNAb in the IgA-only lineage displayed the highest neutralizing capacity despite limited somatic mutation, and delayed viral rebound in humanized mice. bNAbs in all three lineages targeted the N332 glycan supersite. The 2.8-Å resolution cryo-EM structure of 7-269-BG505 SOSIP.664 complex showed a similar pose as 2G12, on an epitope mainly composed of sugar residues comprising the N332 and N295 glycans. Binding and cryo-EM structural analyses showed that antibodies from the two other lineages interact mostly with glycans N332 and N386. Hence, multiple B cell lineages of IgG and IgA bNAbs focused on a unique HIV-1 site of vulnerability can codevelop in HIV-1 viremic controllers.

摘要

解析 HIV-1 广谱中和抗体 (bNAb) 的 B 细胞发生过程对于疫苗设计至关重要。在这里，我们对一名病毒血症控制者的三种不同 B 细胞谱系中的 IgA 和 IgG bNAb 进行了特征分析，其中两种仅包含 IgG+或 IgA+血液记忆 B 细胞；第三种则结合了 IgG 和 IgA 克隆变体。尽管 IgA 谱系中的 7-269 bNAb 的体细胞突变有限，但它具有最高的中和能力，并在人源化小鼠中延迟了病毒反弹。所有三种谱系的 bNAb 均靶向 N332 聚糖超位点。7-269-BG505 SOSIP.664 复合物的 2.8-Å 分辨率冷冻电镜结构显示出与 2G12 相似的构象，其表位主要由包含 N332 和 N295 聚糖的糖残基组成。结合和冷冻电镜结构分析表明，来自另外两个谱系的抗体主要与 N332 和 N386 聚糖相互作用。因此，HIV-1 病毒血症控制者中可共同开发针对 HIV-1 脆弱性独特位点的 IgG 和 IgA bNAb 的多个 B 细胞谱系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6173/8932546/2fe302628f5e/JEM_20212045_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6173/8932546/4cb267a11bb5/JEM_20212045_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6173/8932546/120c5f0c2f74/JEM_20212045_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6173/8932546/5431708a31d5/JEM_20212045_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6173/8932546/189a4c409f8a/JEM_20212045_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6173/8932546/5e4ce169fc1f/JEM_20212045_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6173/8932546/06efc7d3451d/JEM_20212045_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6173/8932546/a47f0c3d4020/JEM_20212045_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6173/8932546/edcf6e717513/JEM_20212045_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6173/8932546/1e3ac982faf5/JEM_20212045_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6173/8932546/2fe302628f5e/JEM_20212045_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6173/8932546/4cb267a11bb5/JEM_20212045_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6173/8932546/120c5f0c2f74/JEM_20212045_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6173/8932546/5431708a31d5/JEM_20212045_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6173/8932546/189a4c409f8a/JEM_20212045_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6173/8932546/5e4ce169fc1f/JEM_20212045_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6173/8932546/06efc7d3451d/JEM_20212045_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6173/8932546/a47f0c3d4020/JEM_20212045_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6173/8932546/edcf6e717513/JEM_20212045_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6173/8932546/1e3ac982faf5/JEM_20212045_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6173/8932546/2fe302628f5e/JEM_20212045_Fig5.jpg

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