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

Cell. 2019 Dec 12;179(7):1636-1646.e15. doi: 10.1016/j.cell.2019.11.003. Epub 2019 Nov 28.


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.

Keywords: B cells; HIV; antibodies; antibody discovery; antibody repertoire; broadly neutralizing antibody; influenza; single cell immunology; systems immunology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing / chemistry
  • Antibodies, Neutralizing / immunology
  • Antigens / chemistry
  • Antigens / immunology
  • Cells, Cultured
  • Epitope Mapping / methods*
  • Epitopes / chemistry*
  • Epitopes / immunology
  • HEK293 Cells
  • HIV Antibodies / chemistry
  • HIV Antibodies / immunology
  • High-Throughput Nucleotide Sequencing / methods
  • High-Throughput Screening Assays / methods
  • Humans
  • Receptors, Antigen, B-Cell / chemistry*
  • Receptors, Antigen, B-Cell / immunology
  • Sequence Analysis, DNA / methods*
  • Single-Cell Analysis / methods*
  • THP-1 Cells


  • Antibodies, Neutralizing
  • Antigens
  • Epitopes
  • HIV Antibodies
  • Receptors, Antigen, B-Cell