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.
Setliff, I; Shiakolas, AR; Pilewski, KA; Murji, AA; Mapengo, RE; Janowska, K; Richardson, S; Oosthuysen, C; Raju, N; Ronsard, L; Kanekiyo, M; Qin, JS; Kramer, KJ; Greenplate, AR; McDonnell, WJ; Graham, BS; Connors, M; Lingwood, D; Acharya, P; Morris, L; Georgiev, IS
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