Rapid and efficient generation of T-cell receptor-like antibodies using chip-based single-cell analysis

摘要

TCR-like antibodies that specifically recognize antigenic peptides presenting on MHC molecules are expected for next-generation cancer immunotherapies [1, 2]. However, generating TCR-like monoclonal antibodies using conventional methods is markedly laborious and inefficient. Only <0.5% of hybridoma clones generated produced TCR-like antibodies [3-7]. Recently, we developed a rapid throughput screen for antibody-secreting cells (ASCs) using a chip-based technique called ISAAC [8, 9] that can detect antigen-specific ASCs in human or rabbit B cells to produce antigen-specific mAbs within a week. Moreover, ISAAC with blocking by nontar-get antigen was confirmed useful for screening mAbs recognizing fine epi-topes such as phosphorylated peptide [9]. This study demonstrates that ISAAC with blocking procedure is useful to generate TCR-like antibodies recognizing the EBV-derived BRLF1 peptide presented on HLA-A24 molecule (BRLF1p/HLA-A24).