Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
- Acharya, Priyamvada
- Bartesaghi, Alberto
- Borgnia, Mario-Juan
- Gobeil, Sophie
- Haynes, Barton Ford
- Henderson, Rory
- Kelsoe, Garnett H.
- Montefiori, David Charles
- Moody, Michael Anthony
- Perfect, John Robert
- Saunders, Kevin O'Neil
- Sempowski, Gregory David
- Wiehe, Kevin J
- Williams, Wilton Bryan
Cited Authors
- 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
Published Date
- May 20, 2021
Published In
Volume / Issue
- 184 / 11
Start / End Page
- 2955 - 2972.e25
PubMed ID
- 34019795
Pubmed Central ID
- PMC8135257
Electronic International Standard Serial Number (EISSN)
- 1097-4172
International Standard Serial Number (ISSN)
- 0092-8674
Digital Object Identifier (DOI)
- 10.1016/j.cell.2021.04.042
Language
- eng