PT  - JOURNAL ARTICLE
AU  - Chao Hu
AU  - Meiying Shen
AU  - Xiaojian Han
AU  - Qian Chen
AU  - Luo Li
AU  - Siyin Chen
AU  - Jing Zhang
AU  - Fengxia Gao
AU  - Wang Wang
AU  - Yingming Wang
AU  - Tingting Li
AU  - Shenglong Li
AU  - Jingjing Huang
AU  - Jianwei Wang
AU  - Ju Zhu
AU  - Dan Chen
AU  - Qingchen Wu
AU  - Kun Tao
AU  - Da Pang
AU  - Aishun Jin
TI  - Identification of Cross-Reactive CD8<sup>+</sup> T Cell Receptors with High Functional Avidity to a SARS-CoV-2 Immunodominant Epitope and Its Natural Mutant Variants
AID  - 10.1101/2020.11.02.364729
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.11.02.364729
4099  - http://biorxiv.org/content/early/2020/11/03/2020.11.02.364729.short
4100  - http://biorxiv.org/content/early/2020/11/03/2020.11.02.364729.full
AB  - Despite the growing knowledge of T cell responses and their epitopes in COVID-19 patients, there is a lack of detailed characterizations for T cell-antigen interactions and T cell functions. Using a peptide library predicted with HLA class I-restriction, specific CD8+ T cell responses were identified in over 75% of COVID-19 convalescent patients. Among the 15 SARS-CoV-2 epitopes identified from the S and N proteins, N361-369 (KTFPPTEPK) was the most dominant epitope. Importantly, we discovered 2 N361-369-specific T cell receptors (TCRs) with high functional avidity, and they exhibited complementary cross-reactivity to reported N361-369 mutant variants. In dendritic cells (DCs) and the lung organoid model, we found that the N361-369 epitope could be processed and endogenously presented to elicit the activation and cytotoxicity of CD8+ T cells ex vivo. Our study evidenced potential mechanisms of cellular immunity to SARS-CoV-2, illuminating natural ways of viral clearance with high relevancy in the vaccine development.Competing Interest StatementPatent has been filed for some of the epitopes presented here.