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

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)...

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Veröffentlicht in:Cell Jg. 179; H. 7; S. 1636
Hauptverfasser: Setliff, Ian, Shiakolas, Andrea R, Pilewski, Kelsey A, Murji, Amyn A, Mapengo, Rutendo E, Janowska, Katarzyna, Richardson, Simone, Oosthuysen, Charissa, Raju, Nagarajan, Ronsard, Larance, Kanekiyo, Masaru, Qin, Juliana S, Kramer, Kevin J, Greenplate, Allison R, McDonnell, Wyatt J, Graham, Barney S, Connors, Mark, Lingwood, Daniel, Acharya, Priyamvada, Morris, Lynn, Georgiev, Ivelin S
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 12.12.2019
Schlagworte:
Antibodies, Neutralizing - chemistry
Antibodies, Neutralizing - immunology
Antigens - chemistry
Antigens - immunology
Cells, Cultured
Epitope Mapping - methods
Epitopes - chemistry
Epitopes - immunology
HEK293 Cells
High-Throughput Nucleotide Sequencing - methods
High-Throughput Screening Assays - methods
HIV Antibodies - chemistry
HIV Antibodies - immunology
Humans
Receptors, Antigen, B-Cell - chemistry
Receptors, Antigen, B-Cell - immunology
Sequence Analysis, DNA - methods
Single-Cell Analysis - methods
THP-1 Cells
influenza
broadly neutralizing antibody
HIV
single cell immunology
antibody discovery
antibodies
B cells
systems immunology
antibody repertoire
ISSN:1097-4172, 1097-4172
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Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1097-4172
1097-4172
DOI:10.1016/j.cell.2019.11.003