T cell-mediated immune response is essential for host defense against viruses, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which has caused a global pandemic. Genetically engineered T cells with antigen-specific T cell receptors (TCR-Ts) are redirected to eliminate target cells via TCRs recognizing peptides bound with major histocompatibility complexes (MHCs). TCR-T cell therapy has proved effective in human trials involving solid tumors, while it is considered promising treatment for infectious diseases. To expedite the identification of functional TCRs and development of TCR-T cell therapy, we established an experimental pipeline to generate functional virus-specific TCR-Ts through coupled analysis of single-cell transcriptomic data and single-cell full length TCR V(D)J sequences. We validated this approach in selecting functional TCRs specific to a cytomegalovirus (CMV) pp65 epitope, NLV_495-503, and published the results recently. In this commentary, we summarized the single-cell work flow and discussed its potential application in developing TCR-T cell therapy against SARS-CoV-2.

TCR-T, Single-cell RNA sequencing, Single-cell TCR V(D)J sequencing, SARS-CoV-2