Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH, USA.
Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Nat Immunol. 2020 Feb;21(2):199-209. doi: 10.1038/s41590-019-0581-0. Epub 2020 Jan 20.
A goal of HIV vaccine development is to elicit antibodies with neutralizing breadth. Broadly neutralizing antibodies (bNAbs) to HIV often have unusual sequences with long heavy-chain complementarity-determining region loops, high somatic mutation rates and polyreactivity. A subset of HIV-infected individuals develops such antibodies, but it is unclear whether this reflects systematic differences in their antibody repertoires or is a consequence of rare stochastic events involving individual clones. We sequenced antibody heavy-chain repertoires in a large cohort of HIV-infected individuals with bNAb responses or no neutralization breadth and uninfected controls, identifying consistent features of bNAb repertoires, encompassing thousands of B cell clones per individual, with correlated T cell phenotypes. These repertoire features were not observed during chronic cytomegalovirus infection in an independent cohort. Our data indicate that the development of numerous B cell lineages with antibody features associated with autoreactivity may be a key aspect in the development of HIV neutralizing antibody breadth.
HIV 疫苗研发的目标是诱导具有中和广度的抗体。HIV 的广谱中和抗体（bnAbs）通常具有不寻常的序列，其重链互补决定区环较长、体细胞突变率高且具有多反应性。HIV 感染个体的一部分会产生此类抗体，但尚不清楚这是否反映了其抗体库的系统性差异，还是涉及单个克隆的罕见随机事件的结果。我们对具有 bnAb 反应或无中和广度的 HIV 感染者以及未感染者的大样本队列中的抗体重链库进行了测序，确定了 bnAb 库的一致特征，每个个体包含数千个 B 细胞克隆，并伴有相关的 T 细胞表型。在另一项独立队列的慢性巨细胞病毒感染中未观察到这些库特征。我们的数据表明，具有与自身反应性相关的抗体特征的大量 B 细胞谱系的发展可能是 HIV 中和抗体广度发展的关键方面。
