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

• Published in: Cell Vol. 179; no. 7; pp. 1636 - 1646.e15
• 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 Elsevier Inc 12.12.2019
• Subjects: antibodies; Antibodies, Neutralizing - chemistry; Antibodies, Neutralizing - immunology; antibody discovery; antibody repertoire; antigens; Antigens - chemistry; Antigens - immunology; B cells; B-lymphocytes; broadly neutralizing antibodies; broadly neutralizing antibody; Cells, Cultured; DNA barcoding; Epitope Mapping - methods; Epitopes - chemistry; Epitopes - immunology; HEK293 Cells; high-throughput nucleotide sequencing; High-Throughput Nucleotide Sequencing - methods; High-Throughput Screening Assays - methods; HIV; HIV Antibodies - chemistry; HIV Antibodies - immunology; HIV infections; Human immunodeficiency virus; Humans; immune response; influenza; Receptors, Antigen, B-Cell - chemistry; Receptors, Antigen, B-Cell - immunology; Sequence Analysis, DNA - methods; single cell immunology; Single-Cell Analysis - methods; systems immunology; THP-1 Cells; vaccination; vaccine development; influenza; broadly neutralizing antibody; single cell immunology; HIV; antibody discovery; antibodies; B cells; systems immunology; antibody repertoire
• ISSN: 0092-8674; 1097-4172; 1097-4172
• DOI: 10.1016/j.cell.2019.11.003

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. [Display omitted] •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.