@article{Hu2022, 
author = {Chao Hu and Meiying Shen and Xiaojian Han and Qian Chen and Luo Li and Siyin Chen and Jing Zhang and Fengxia Gao and Wang Wang and Yingming Wang and Tingting Li and Shenglong Li and Jingjing Huang and Jianwei Wang and Ju Zhu and Dan Chen and Qingchen Wu and Kun Tao and Da Pang and Aishun Jin},
title = {Identification of cross-reactive CD8+ T cell receptors with high functional avidity to a SARS-CoV-2 immunodominant epitope and its natural mutant variants},
year = {2022},
journal = {Genes & Diseases},
volume = {9},
number = {1},
pages = {216-229},
keywords = {CD8+T cell, HLA class Ⅰ, Lung organoid, SARS-CoV-2, T cell epitope, TCR},
url = {https://www.sciopen.com/article/10.1016/j.gendis.2021.05.006},
doi = {10.1016/j.gendis.2021.05.006},
abstract = {Despite the growing knowledge of T cell responses in COVID-19 patients, there is a lack of detailed characterizations for T cell-antigen interactions and T cell functions. Here, with a predicted peptide library from SARS-CoV-2 S and N proteins, we found that specific CD8+ T cell responses were identified in over 75% of COVID-19 convalescent patients (15/20) and an epitope from the N protein, N361-369 (KTFPPTEPK), was the most dominant epitope from our selected peptide library. Importantly, we discovered 2 N361-369-specific T cell receptors (TCRs) with high functional avidity that were independent of the CD8 co-receptor. These TCRs exhibited complementary cross-reactivity to several presently reported N361-369 mutant variants, as to the wild-type epitope. Further, the natural functions of these TCRs in the cytotoxic immunity against SARS-CoV-2 were determined with dendritic cells (DCs) and the lung organoid model. We found that the N361-369 epitope could be normally processed and endogenously presented by these different types of antigen presenting cells, to elicit successful activation and effective cytotoxicity of CD8+ T cells ex vivo. Our study evidenced potential mechanisms of cellular immunity to SARS-CoV-2, and illuminated potential ways of viral clearance in COVID-19 patients. These results indicate that utilizing CD8-independent TCRs against SARS-CoV-2-associated antigens may provide functional superiority that is beneficial for the adoptive cell immunotherapies based on natural or genetically engineered T cells. Additionally, this information is highly relevant for the development of the next-generation vaccines with protections against continuously emerged SARS-CoV-2 mutant strains.}
}