小柯机器人

美国杜克人类疫苗研究所Barton F. Haynes、Priyamvada Acharya和Wilton B. Williams小组的最新研究揭示了fab -二聚聚糖反应性抗体具有天然抗体（Abs）的结构特征。相关论文在线发表在2021年5月20日出版的《细胞》杂志上。

研究人员先前利用糖基化的HIV-1包膜（Env）作为模式抗原探究了恒河猴和人聚糖反应性B细胞的进化。2G12是一种广泛的中和抗体（bnAb），它使用独特的重链（VH）结构域交换结构，把地域不同HIV-1菌株Env上的保守聚糖贴片作为靶点，从而导致片段抗原结合（Fab）二聚化。

研究人员描述了猿猴-人类免疫缺陷病毒（SHIV）感染猕猴无VH交换结构域HIV-1 Env Fab-二聚聚糖（FDG）的反应性bnAb。FDG Abs还识别多种病原体上的细胞表面聚糖，包括酵母菌和严重急性呼吸系统综合症冠状病毒2（SARS-CoV-2）。 FDG前体通过猕猴中的含糖免疫原扩增，并广泛存在于未感染HIV-1的人体中。

此外，FDG前体主要存在IgM⁺ IgD⁺ CD27⁺突变，因此表明它们是由抗原刺激IgM⁺池或边缘区B细胞产生。

据介绍，Abs可以靶向病原体表面的宿主聚糖。

附：英文原文

Title: Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies

Author: Wilton B. Williams, R. Ryan Meyerhoff, R.J. Edwards, Hui Li, Kartik Manne, Nathan I. Nicely, Rory Henderson, Ye Zhou, Katarzyna Janowska, Katayoun Mansouri, Sophie Gobeil, Tyler Evangelous, Bhavna Hora, Madison Berry, A. Yousef Abuahmad, Jordan Sprenz, Margaret Deyton, Victoria Stalls, Megan Kopp, Allen L. Hsu, Mario J. Borgnia, Guillaume B.E. Stewart-Jones, Matthew S. Lee, Naomi Bronkema, M. Anthony Moody, Kevin Wiehe, Todd Bradley, S. Munir Alam, Robert J. Parks, Andrew Foulger, Thomas Oguin, Gregory D. Sempowski, Mattia Bonsignori, Celia C. LaBranche, David C. Montefiori, Michael Seaman, Sampa Santra, John Perfect, Joseph R. Francica, Geoffrey M. Lynn, Baptiste Aussedat, William E. Walkowicz, Richard Laga, Garnett Kelsoe, Kevin O. Saunders, Daniela Fera, Peter D. Kwong, Robert A. Seder, Alberto Bartesaghi, George M. Shaw, Priyamvada Acharya, Barton F. Haynes

Issue&Volume: 2021-05-20

Abstract: Natural antibodies (Abs) can target host glycans on the surface of pathogens. We studiedthe evolution of glycan-reactive B cells of rhesus macaques and humans using glycosylatedHIV-1 envelope (Env) as a model antigen. 2G12 is a broadly neutralizing Ab (bnAb)that targets a conserved glycan patch on Env of geographically diverse HIV-1 strainsusing a unique heavy-chain (VH) domain-swapped architecture that results in fragment antigen-binding (Fab) dimerization.Here, we describe HIV-1 Env Fab-dimerized glycan (FDG)-reactive bnAbs without VH-swapped domains from simian-human immunodeficiency virus (SHIV)-infected macaques.FDG Abs also recognized cell-surface glycans on diverse pathogens, including yeastand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike. FDG precursorswere expanded by glycan-bearing immunogens in macaques and were abundant in HIV-1-naivehumans. Moreover, FDG precursors were predominately mutated IgM+IgD+CD27+, thus suggesting that they originated from a pool of antigen-experienced IgM+ or marginal zone B cells.

DOI: 10.1016/j.cell.2021.04.042

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00577-8