Author: 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.
Title: Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies Cord-id: jzic44f0 Document date: 2021_5_27
ID: jzic44f0
Snippet: 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(H)) domain-swapped architecture that results in fragment antigen-binding (Fab) dimerization. Here, we describe HIV-1 Env Fab
Document: 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(H)) 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(H)-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.
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