Literature DB >> 34019795

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

Wilton B Williams1, R Ryan Meyerhoff2, R J Edwards2, Hui Li3, Kartik Manne4, Nathan I Nicely4, Rory Henderson2, Ye Zhou5, Katarzyna Janowska4, Katayoun Mansouri4, Sophie Gobeil4, Tyler Evangelous4, Bhavna Hora4, Madison Berry4, A Yousef Abuahmad4, Jordan Sprenz4, Margaret Deyton4, Victoria Stalls4, Megan Kopp4, Allen L Hsu6, Mario J Borgnia6, Guillaume B E Stewart-Jones7, Matthew S Lee8, Naomi Bronkema9, M Anthony Moody10, Kevin Wiehe2, Todd Bradley4, S Munir Alam2, Robert J Parks4, Andrew Foulger4, Thomas Oguin4, Gregory D Sempowski2, Mattia Bonsignori2, Celia C LaBranche11, David C Montefiori12, Michael Seaman13, Sampa Santra13, John Perfect14, Joseph R Francica7, Geoffrey M Lynn15, Baptiste Aussedat16, William E Walkowicz16, Richard Laga17, Garnett Kelsoe18, Kevin O Saunders19, Daniela Fera9, Peter D Kwong7, Robert A Seder7, Alberto Bartesaghi20, George M Shaw3, Priyamvada Acharya21, Barton F Haynes22.   

Abstract

Natural antibodies (Abs) can target host glycans on the surface of pathogens. We studied the evolution of glycan-reactive B cells of rhesus macaques and humans using glycosylated HIV-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 strains using 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 yeast and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike. FDG precursors were expanded by glycan-bearing immunogens in macaques and were abundant in HIV-1-naive humans. 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.
Copyright © 2021 Elsevier Inc. All rights reserved.

Entities:  

Keywords:  FDG Abs; Fab dimerization; HIV-1 Env glycans; IgM-memory B cells; SARS-CoV-2 spike glycans; glycan-dependent Ab binding; marginal zone B cells; natural Abs

Mesh：

Substances：

Year:  2021        PMID： 34019795      PMCID： PMC8135257          DOI： 10.1016/j.cell.2021.04.042

Source DB:  PubMed          Journal:  Cell        ISSN： 0092-8674            Impact factor:   41.582


  121 in total

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