A single-cell approach to engineer CD8+ T cells targeting cytomegalovirus
Fei Wang, Qumiao Xu, Zhenkun Zhuang, Ziyi Li, Qianqian Gao, Yaling Huang, Yonglun Luo, Xiuqing Zhang, Linnan Zhu & Cheng-chi Chao
Cellular & Molecular Immunology (2020)Cite this article
T lymphocytes are crucial for antiviral responses and provide a promising repertoire for potential therapies of viral diseases such as cytomegalovirus (CMV) infection1 and the ongoing COVID-19 pandemic caused by SARS-CoV-2.2 CMV-related diseases occur once the host immune system is impaired or lacks a protective repertoire of virus-specific T lymphocytes.3 Adoptive transfer of T-cell receptor (TCR)-engineered T cells (TCR-Ts) provides an encouraging alternative treatment option for patients with CMV reactivation.4 However, generating TCR-Ts requires the identification of epitope-specific and functional TCR pairs. Modern single-cell sequencing techniques open up the ability to unravel TCR repertoires,5 which offers a potential opportunity to screen functional TCR pairs for TCR-T therapy. Here, we report an efficient approach that combines ex vivo CD8+ T-cell stimulation with single-cell RNA and TCR V(D)J sequencing to identify CMV-specific TCRs for generating TCR-Ts.
