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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Bibliographic Details
Published in:Cell Vol. 179; no. 7; p. 1636
Main Authors: 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
Language:English
Published: United States 12.12.2019
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ISSN:1097-4172, 1097-4172
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Summary: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.
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ISSN:1097-4172
1097-4172
DOI:10.1016/j.cell.2019.11.003