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


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 , . Cell. 2019 11 26; ().


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.