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

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 o...

Full description

Saved in:

Bibliographic Details
Published in:	Cell Vol. 184; no. 11; p. 2955
Main Authors:	Williams, Wilton B, Meyerhoff, R Ryan, Edwards, R J, Li, Hui, Manne, Kartik, Nicely, Nathan I, Henderson, Rory, Zhou, Ye, Janowska, Katarzyna, Mansouri, Katayoun, Gobeil, Sophie, Evangelous, Tyler, Hora, Bhavna, Berry, Madison, Abuahmad, A Yousef, Sprenz, Jordan, Deyton, Margaret, Stalls, Victoria, Kopp, Megan, Hsu, Allen L, Borgnia, Mario J, Stewart-Jones, Guillaume B E, Lee, Matthew S, Bronkema, Naomi, Moody, M Anthony, Wiehe, Kevin, Bradley, Todd, Alam, S Munir, Parks, Robert J, Foulger, Andrew, Oguin, Thomas, Sempowski, Gregory D, Bonsignori, Mattia, LaBranche, Celia C, Montefiori, David C, Seaman, Michael, Santra, Sampa, Perfect, John, Francica, Joseph R, Lynn, Geoffrey M, Aussedat, Baptiste, Walkowicz, William E, Laga, Richard, Kelsoe, Garnett, Saunders, Kevin O, Fera, Daniela, Kwong, Peter D, Seder, Robert A, Bartesaghi, Alberto, Shaw, George M, Acharya, Priyamvada, Haynes, Barton F
Format:	Journal Article
Language:	English
Published:	United States 27.05.2021
Subjects:	Animals Antibodies, Neutralizing - immunology B-Lymphocytes - immunology Broadly Neutralizing Antibodies - immunology COVID-19 - immunology Dimerization env Gene Products, Human Immunodeficiency Virus - chemistry env Gene Products, Human Immunodeficiency Virus - genetics env Gene Products, Human Immunodeficiency Virus - immunology Epitopes - immunology Glycosylation HIV Antibodies - immunology HIV Infections - immunology HIV-1 - immunology Humans Immunoglobulin Fab Fragments - chemistry Immunoglobulin Fab Fragments - immunology Macaca mulatta Polysaccharides - chemistry Polysaccharides - immunology Receptors, Antigen, B-Cell - chemistry SARS-CoV-2 - immunology Simian Immunodeficiency Virus - genetics Simian Immunodeficiency Virus - immunology Spike Glycoprotein, Coronavirus - immunology Vaccines - immunology marginal zone B cells SARS-CoV-2 spike glycans IgM-memory B cells natural Abs Fab dimerization FDG Abs HIV-1 Env glycans glycan-dependent Ab binding
ISSN:	1097-4172, 1097-4172
Online Access:	Get more information
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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 (V ) domain-swapped architecture that results in fragment antigen-binding (Fab) dimerization. Here, we describe HIV-1 Env Fab-dimerized glycan (FDG)-reactive bnAbs without V -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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1097-4172 1097-4172
DOI:	10.1016/j.cell.2021.04.042