1. High-Throughput Mapping of B Cell Receptor Sequences to Antigen Specificity.
- Author
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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, and Morris, Lynn
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B cell receptors , *ANTIGEN receptors , *HIV antibodies , *B cells , *IMMUNE response , *VACCINE effectiveness - Abstract
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. • LIBRA-seq: high-throughput mapping of BCR sequence to antigen specificity • Identified HIV- and influenza-specific B cells in two HIV-infected subjects • Predicted antigen reactivity for thousands of single B cells • Identified a previously unknown broadly neutralizing HIV antibody LIBRA-seq enables high-throughput mapping of B cell receptor sequence to antigen specificity at the single-cell level. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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