High-Throughput B Cell Epitope Determination by Next-Generation Sequencing.
HIV
epitope
monoclonal antibody
next generation sequencing (NGS)
single cell
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2022
2022
Historique:
received:
15
01
2022
accepted:
14
02
2022
entrez:
11
4
2022
pubmed:
12
4
2022
medline:
13
4
2022
Statut:
epublish
Résumé
Development of novel technologies for the discovery of human monoclonal antibodies has proven invaluable in the fight against infectious diseases. Among the diverse antibody repertoires elicited by infection or vaccination, often only rare antibodies targeting specific epitopes of interest are of potential therapeutic value. Current antibody discovery efforts are capable of identifying B cells specific for a given antigen; however, epitope specificity information is usually only obtained after subsequent monoclonal antibody production and characterization. Here we describe LIBRA-seq with epitope mapping, a next-generation sequencing technology that enables residue-level epitope determination for thousands of single B cells simultaneously. By utilizing an antigen panel of point mutants within the HIV-1 Env glycoprotein, we identified and confirmed antibodies targeting multiple sites of vulnerability on Env, including the CD4-binding site and the V3-glycan site. LIBRA-seq with epitope mapping is an efficient tool for high-throughput identification of antibodies against epitopes of interest on a given antigen target.
Identifiants
pubmed: 35401559
doi: 10.3389/fimmu.2022.855772
pmc: PMC8984479
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Neutralizing
0
Antigens
0
Epitopes, B-Lymphocyte
0
HIV Antibodies
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
855772Subventions
Organisme : NIAID NIH HHS
ID : R01 AI152693
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008320
Pays : United States
Informations de copyright
Copyright © 2022 Walker, Shiakolas, Venkat, Liu, Wall, Raju, Pilewski, Setliff, Murji, Gillespie, Makoah, Kanekiyo, Connors, Morris and Georgiev.
Déclaration de conflit d'intérêts
IG and AS are co-founders of AbSeek Bio. The Georgiev laboratory at Vanderbilt University Medical Center has received unrelated funding from Takeda Pharmaceuticals. LMW, ARS, RV, KAP, IS, and ISG are inventors on patent applications related to the LIBRA-seq technology and/or antibody sequences presented in this manuscript. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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