Sequencing BCR–antigen interactions

B-cell receptor (BCR) sequencing offers an important approach for examining immune responses to infection.Antigen-specific BCRs are often sequenced following singlecell sorting with antigen baits.However, this strategy is low throughput.Setliff et al. developed LIBRA-seq for linking BCR sequences to antigen specificity via nextgeneration sequencing.Single B cells are mixed with a set of DNA-barcoded antigens that are used to sort antigen-positive B cells.Then the sorted B cells are encapsulated with oligonucleotide-labeled beads for indexing both BCR transcripts and antigen barcodes, which allows sequencing both the antigen barcodes and BCR sequences, thus providing a direct readout of BCR-antigen binding interactions.This transformation to sequencing readouts allows high-throughput mapping of BCR sequences to antigen specificity.The researchers applied LIBRA-seq to peripheral blood mononuclear cells collected from two people infected with HIV and identified HIV-and influenza-specific antibodies.