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), 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.
Duke Scholars
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- THP-1 Cells
- Single-Cell Analysis
- Sequence Analysis, DNA
- Receptors, Antigen, B-Cell
- Humans
- High-Throughput Screening Assays
- High-Throughput Nucleotide Sequencing
- HIV Antibodies
- HEK293 Cells
- Epitopes
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- THP-1 Cells
- Single-Cell Analysis
- Sequence Analysis, DNA
- Receptors, Antigen, B-Cell
- Humans
- High-Throughput Screening Assays
- High-Throughput Nucleotide Sequencing
- HIV Antibodies
- HEK293 Cells
- Epitopes