High-Throughput Mapping of B Cell Receptor Sequences to Antigen Specificity.

Antibodies, Neutralizing / chemistry Antigens / chemistry Cells, Cultured Epitope Mapping / methods Epitopes / chemistry HEK293 Cells HIV Antibodies / chemistry High-Throughput Nucleotide Sequencing / methods High-Throughput Screening Assays / methods Humans Receptors, Antigen, B-Cell / chemistry Sequence Analysis, DNA / methods Single-Cell Analysis / methods THP-1 Cells
B cells HIV antibodies antibody discovery antibody repertoire broadly neutralizing antibody influenza single cell immunology systems immunology

Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
12 12 2019
Historique:
received: 27 03 2019
revised: 28 08 2019
accepted: 31 10 2019
pubmed: 4 12 2019
medline: 6 6 2020
entrez: 3 12 2019
Statut: ppublish

Résumé

B cell receptor (BCR) sequencing is a powerful tool for interrogating immune responses to infection and vaccination, but it provides limited information about the antigen specificity of the sequenced BCRs. Here, we present LIBRA-seq (linking B cell receptor to antigen specificity through sequencing), a technology for high-throughput mapping of paired heavy- and light-chain BCR sequences to their cognate antigen specificities. B cells are mixed with a panel of DNA-barcoded antigens so that both the antigen barcode(s) and BCR sequence are recovered via single-cell next-generation sequencing. Using LIBRA-seq, we mapped the antigen specificity of thousands of B cells from two HIV-infected subjects. The predicted specificities were confirmed for a number of HIV- and influenza-specific antibodies, including known and novel broadly neutralizing antibodies. LIBRA-seq will be an integral tool for antibody discovery and vaccine development efforts against a wide range of antigen targets.

Identifiants

DOI: 10.1016/j.cell.2019.11.003 PMID: 31787378 PMC: PMC7158953
pubmed: 31787378
pii: S0092-8674(19)31224-3
doi: 10.1016/j.cell.2019.11.003
pmc: PMC7158953
mid: NIHMS1542046
pii:
doi:

Substances chimiques

Antibodies, Neutralizing 0
Antigens 0
Epitopes 0
HIV Antibodies 0
Receptors, Antigen, B-Cell 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

1636-1646.e15

Subventions

Organisme : NIGMS NIH HHS
ID : T32 GM008320
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK058404
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY008126
Pays : United States
Organisme : NIDA NIH HHS
ID : DP2 DA042422
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA068485
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI145687
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI137057
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI131722
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI136677
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI112541
Pays : United States
Organisme : NCRR NIH HHS
ID : G20 RR030956
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI124378
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR024975
Pays : United States

Informations de copyright

Copyright © 2019 Elsevier Inc. All rights reserved.

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Auteurs

Ian Setliff (I)

Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Program in Chemical and Physical Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

Andrea R Shiakolas (AR)

Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

Kelsey A Pilewski (KA)

Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

Amyn A Murji (AA)

Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

Rutendo E Mapengo (RE)

National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa.

Katarzyna Janowska (K)

Division of Structural Biology, Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.

Simone Richardson (S)

National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa; Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2000, South Africa.

Charissa Oosthuysen (C)

National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa; Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2000, South Africa.

Nagarajan Raju (N)

Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

Larance Ronsard (L)

Ragon Institute of Massachusetts General Hospital, Harvard and Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Masaru Kanekiyo (M)

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.

Juliana S Qin (JS)

Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

Kevin J Kramer (KJ)

Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

Allison R Greenplate (AR)

Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

Wyatt J McDonnell (WJ)

Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Center for Translational and Clinical Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

Barney S Graham (BS)

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.

Mark Connors (M)

National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.

Daniel Lingwood (D)

Ragon Institute of Massachusetts General Hospital, Harvard and Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Priyamvada Acharya (P)

Division of Structural Biology, Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA.

Lynn Morris (L)

National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa; Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2000, South Africa; Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban 4041, South Africa.

Ivelin S Georgiev (IS)

Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Electrical Engineering and Computer Science, Vanderbilt University, Nashville, TN 37232, USA; Center for Structural Biology, Vanderbilt University, Nashville, TN 37232, USA. Electronic address: ivelin.georgiev@vanderbilt.edu.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps neutralisants › High-Throughput Mapping of B Cell Receptor...
questionsmedicales.fr › Facteurs biologiques › Antigènes › High-Throughput Mapping of B Cell Receptor...
questionsmedicales.fr › Cellules › Cellules cultivées › High-Throughput Mapping of B Cell Receptor...
questionsmedicales.fr › Techniques d'investigation › Techniques de sonde moléculaire › Cartographie d'interactions entre protéines › Cartographie épitopique › High-Throughput Mapping of B Cell Receptor...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Épitopes › High-Throughput Mapping of B Cell Receptor...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules HEK293 › High-Throughput Mapping of B Cell Receptor...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps antiviraux › Anticorps antideltarétrovirus › Anticorps anti-VIH › High-Throughput Mapping of B Cell Receptor...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Séquençage nucléotidique à haut débit › High-Throughput Mapping of B Cell Receptor...
questionsmedicales.fr › Techniques d'investigation › Tests de criblage à haut débit › High-Throughput Mapping of B Cell Receptor...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › High-Throughput Mapping of B Cell Receptor...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteurs aux antigènes › Récepteurs pour l'antigène des lymphocytes B › High-Throughput Mapping of B Cell Receptor...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ADN › High-Throughput Mapping of B Cell Receptor...
questionsmedicales.fr › Techniques d'investigation › Techniques cytologiques › Analyse sur cellule unique › High-Throughput Mapping of B Cell Receptor...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Cellules THP-1 › High-Throughput Mapping of B Cell Receptor...