Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies Journal Article
| Authors: | Williams, W. B.; Meyerhoff, R. R.; Edwards, R. J.; Li, H.; Manne, K.; Nicely, N. I.; Henderson, R.; Zhou, Y.; Janowska, K.; Mansouri, K.; Gobeil, S.; Evangelous, T.; Hora, B.; Berry, M.; Abuahmad, A. Y.; Sprenz, J.; Deyton, M.; Stalls, V.; Kopp, M.; Hsu, A. L.; Borgnia, M. J.; Stewart-Jones, G. B. E.; Lee, M. S.; Bronkema, N.; Moody, M. A.; Wiehe, K.; Bradley, T.; Alam, S. M.; Parks, R. J.; Foulger, A.; Oguin, T.; Sempowski, G. D.; Bonsignori, M.; LaBranche, C. C.; Montefiori, D. C.; Seaman, M.; Santra, S.; Perfect, J.; Francica, J. R.; Lynn, G. M.; Aussedat, B.; Walkowicz, W. E.; Laga, R.; Kelsoe, G.; Saunders, K. O.; Fera, D.; Kwong, P. D.; Seder, R. A.; Bartesaghi, A.; Shaw, G. M.; Acharya, P.; Haynes, B. F. |
| Article Title: | Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies |
| 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 (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. © 2021 Elsevier Inc. |
| Keywords: | genetics; human immunodeficiency virus infection; animal; animals; b lymphocyte; b-lymphocytes; immunology; chemistry; epitope; glycosylation; dimerization; polysaccharide; polysaccharides; simian immunodeficiency virus; macaca mulatta; lymphocyte antigen receptor; vaccine; hiv infections; vaccines; human immunodeficiency virus 1; hiv-1; epitopes; rhesus monkey; immunoglobulin f(ab) fragment; receptors, antigen, b-cell; neutralizing antibody; antibodies, neutralizing; hiv antibodies; virus envelope protein; immunoglobulin fab fragments; humans; human; human immunodeficiency virus antibody; broadly neutralizing antibodies; covid-19; sars-cov-2; coronavirus spike glycoprotein; fab dimerization; fdg abs; glycan-dependent ab binding; hiv-1 env glycans; igm-memory b cells; marginal zone b cells; natural abs; sars-cov-2 spike glycans; spike protein, sars-cov-2; env gene products, human immunodeficiency virus; spike glycoprotein, coronavirus |
| Journal Title: | Cell |
| Volume: | 184 |
| Issue: | 11 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2021-05-27 |
| Start Page: | 2955 |
| End Page: | 2972.e25 |
| Language: | English |
| DOI: | 10.1016/j.cell.2021.04.042 |
| PUBMED: | 34019795 |
| PROVIDER: | scopus |
| PMCID: | PMC8135257 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 July 2021 -- Source: Scopus |
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