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

WB. Williams, RR. Meyerhoff, RJ. Edwards, H. Li, K. Manne, NI. Nicely, R. Henderson, Y. Zhou, K. Janowska, K. Mansouri, S. Gobeil, T. Evangelous, B. Hora, M. Berry, AY. Abuahmad, J. Sprenz, M. Deyton, V. Stalls, M. Kopp, AL. Hsu, MJ. Borgnia,...

. 2021 ; 184 (11) : 2955-2972.e25. [pub] 20210520

Language English Country United States

Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc21018556

Grant support
UM1 AI100645 NIAID NIH HHS - United States
HHSN272201800004C NIAID NIH HHS - United States
UC6 AI058607 NIAID NIH HHS - United States
R01 AI140897 NIAID NIH HHS - United States
P01 AI131251 NIAID NIH HHS - United States
U24 GM129539 NIGMS NIH HHS - United States
R01 AI120801 NIAID NIH HHS - United States
T32 GM007171 NIGMS NIH HHS - United States
R01 AI145687 NIAID NIH HHS - United States
R01 AI128832 NIAID NIH HHS - United States

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.

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