Journal
CELL
Volume 179, Issue 7, Pages 1636-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2019.11.003
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Funding
- CTSA grant [5UL1 RR024975-03]
- Vanderbilt Ingram Cancer Center [P30 CA68485]
- Vanderbilt Vision Center [P30 EY08126]
- NIH/NCRR [G20 RR030956]
- Vanderbilt Digestive Disease Research Center [DK058404]
- NIH [R01 AI131722, T32 GM008320-30, T32 AI112541, H3A-U01, 1U01AI136677, R01 AI145687]
- Vanderbilt Trans-Institutional Program (TIPs
- Integrating Structural with Big Data for Next-Generation Vaccines'')
- NIH Intramural Research Program
- South African Medical Research Council
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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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