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Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies.
- Source :
-
Cell [Cell] 2021 May 27; Vol. 184 (11), pp. 2955-2972.e25. Date of Electronic Publication: 2021 May 20. - Publication Year :
- 2021
-
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 (V <subscript>H</subscript> ) 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 <subscript>H</subscript> -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 <superscript>+</superscript> IgD <superscript>+</superscript> CD27 <superscript>+</superscript> , thus suggesting that they originated from a pool of antigen-experienced IgM <superscript>+</superscript> or marginal zone B cells.<br />Competing Interests: Declaration of interests B.A. and W.E.W. are co-founders of Chemitope Technologies, and G.M.L. is a founder of Avidea Technologies that now commercially produce peptides used in our HIV-1 vaccination regimen. The remaining authors declare no competing interests.<br /> (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
B-Lymphocytes immunology
Broadly Neutralizing Antibodies immunology
COVID-19 immunology
Dimerization
Epitopes immunology
Glycosylation
HIV Antibodies immunology
HIV Infections immunology
Humans
Immunoglobulin Fab Fragments chemistry
Macaca mulatta
Polysaccharides chemistry
Receptors, Antigen, B-Cell chemistry
Simian Immunodeficiency Virus genetics
Vaccines immunology
env Gene Products, Human Immunodeficiency Virus chemistry
env Gene Products, Human Immunodeficiency Virus genetics
Antibodies, Neutralizing immunology
HIV-1 immunology
Immunoglobulin Fab Fragments immunology
Polysaccharides immunology
SARS-CoV-2 immunology
Simian Immunodeficiency Virus immunology
Spike Glycoprotein, Coronavirus immunology
env Gene Products, Human Immunodeficiency Virus immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4172
- Volume :
- 184
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 34019795
- Full Text :
- https://doi.org/10.1016/j.cell.2021.04.042