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

Publication ,  Journal Article
Williams, WB; Meyerhoff, RR; Edwards, RJ; Li, H; Manne, K; Nicely, NI; Henderson, R; Zhou, Y; Janowska, K; Mansouri, K; Gobeil, S; Hora, B ...
Published in: Cell
May 27, 2021
Published version (DOI) Open Access Copy (Duke) Link to item

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.

Duke Scholars

S. Munir Alam
Author S. Munir Alam Medicine, Duke Human Vaccine Institute
Robert R Meyerhoff
Author Robert R Meyerhoff Radiology, Interventional Radiology
Wilton Bryan Williams
Author Wilton Bryan Williams Surgery, Surgical Sciences
Rory Henderson
Author Rory Henderson Medicine, Duke Human Vaccine Institute
Mario-Juan Borgnia
Author Mario-Juan Borgnia Biochemistry
Michael Anthony Moody
Author Michael Anthony Moody Pediatrics, Infectious Diseases
Kevin J Wiehe
Author Kevin J Wiehe Medicine, Duke Human Vaccine Institute
David Charles Montefiori
Author David Charles Montefiori Surgery, Surgical Sciences
John Robert Perfect
Author John Robert Perfect Medicine, Infectious Diseases
Garnett H. Kelsoe
Author Garnett H. Kelsoe Integrative Immunobiology
Kevin O'Neil Saunders
Author Kevin O'Neil Saunders Surgery, Surgical Sciences
Alberto Bartesaghi
Author Alberto Bartesaghi Computer Science
Priyamvada Acharya
Author Priyamvada Acharya Surgery, Surgical Sciences
Barton Ford Haynes
Author Barton Ford Haynes Medicine, Duke Human Vaccine Institute
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Published In

Cell

DOI

10.1016/j.cell.2021.04.042

EISSN

1097-4172

Publication Date

May 27, 2021

Volume

184

Issue

11

Start / End Page

2955 / 2972.e25

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Vaccines
  • Spike Glycoprotein, Coronavirus
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • SARS-CoV-2
  • Receptors, Antigen, B-Cell
  • Polysaccharides
  • Macaca mulatta
  • Immunoglobulin Fab Fragments
 

Citation

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MLA
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Williams, W. B., Meyerhoff, R. R., Edwards, R. J., Li, H., Manne, K., Nicely, N. I., … Haynes, B. F. (2021). Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies. Cell, 184(11), 2955-2972.e25. https://doi.org/10.1016/j.cell.2021.04.042
Williams, Wilton B., R Ryan Meyerhoff, R. J. Edwards, Hui Li, Kartik Manne, Nathan I. Nicely, Rory Henderson, et al. “Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies.” Cell 184, no. 11 (May 27, 2021): 2955-2972.e25. https://doi.org/10.1016/j.cell.2021.04.042.
Williams WB, Meyerhoff RR, Edwards RJ, Li H, Manne K, Nicely NI, et al. Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies. Cell. 2021 May 27;184(11):2955-2972.e25.
Williams, Wilton B., et al. “Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies.” Cell, vol. 184, no. 11, May 2021, pp. 2955-2972.e25. Pubmed, doi:10.1016/j.cell.2021.04.042.
Williams WB, Meyerhoff RR, Edwards RJ, Li H, Manne K, Nicely NI, Henderson R, Zhou Y, Janowska K, Mansouri K, Gobeil S, Evangelous T, Hora B, Berry M, Abuahmad AY, Sprenz J, Deyton M, Stalls V, Kopp M, Hsu AL, Borgnia MJ, Stewart-Jones GBE, Lee MS, Bronkema N, Moody MA, Wiehe K, Bradley T, Alam SM, Parks RJ, Foulger A, Oguin T, Sempowski GD, Bonsignori M, LaBranche CC, Montefiori DC, Seaman M, Santra S, Perfect J, Francica JR, Lynn GM, Aussedat B, Walkowicz WE, Laga R, Kelsoe G, Saunders KO, Fera D, Kwong PD, Seder RA, Bartesaghi A, Shaw GM, Acharya P, Haynes BF. Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies. Cell. 2021 May 27;184(11):2955-2972.e25.
Journal cover image

Published In

Cell

DOI

10.1016/j.cell.2021.04.042

EISSN

1097-4172

Publication Date

May 27, 2021

Volume

184

Issue

11

Start / End Page

2955 / 2972.e25

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Vaccines
  • Spike Glycoprotein, Coronavirus
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • SARS-CoV-2
  • Receptors, Antigen, B-Cell
  • Polysaccharides
  • Macaca mulatta
  • Immunoglobulin Fab Fragments