@article {Jin2021.04.01.438020, author = {Xiaoxiao Jin and Ding Yan and Sun Shihui and Xinyi Wang and Zining Zhou and Xiaotao Liu and Miaomiao Li and Xian Chen and Anran Shen and Yandan Wu and Bicheng Liu and Jianqiong Zhang and Jian Li and Yi Yang and Haibo Qiu and Chuanlai Shen and Yuxian He and Guangyu Zhao}, title = {Screening of HLA-A restricted T cell epitopes of SARS-CoV-2 and induction of CD8+ T cell responses in HLA-A transgenic mice}, elocation-id = {2021.04.01.438020}, year = {2021}, doi = {10.1101/2021.04.01.438020}, publisher = {Cold Spring Harbor Laboratory}, abstract = {While SARS-CoV-2-specific T cells have been characterized to play essential roles in host immune protection in COVID-19 patients, few researches focus on the functional validation of T cell epitopes and development of vaccines inducing specific T cell responses. In this study, 120 CD8+ T cell epitopes from E, M, N, S and RdRp proteins of SARS-CoV-2 were validated by on-silicon prediction, DC-peptide-PBL costimulation with healthy donors{\textquoteright} PBMCs and HLA-A molecule competitive binding experiments. Among them, 110, 15, 6, 14 and 12 epitopes were highly homologous with SARS-CoV, OC43, NL63, HKU1, and 229E, respectively. Thirty-one epitopes restricted by HLA-A2 molecule were used to generate peptide cocktail vaccines in combination with Poly(I:C), R848 or polylactic-co-glycolic acid nanoparticles, which elicited robust specific CD8+ T cell responses in wild-type and HLA-A2/DR1 transgenic mice. Seven of the 31 epitopes were found to be cross-presented by HLA-A2 and H-2K/Db molecules. These data have provided a library of SARS-CoV-2 CD8+ T cell epitopes which restricted by a series of high-frequency HLA-A allotypes and covered broad population in Asia, and initially confirmed the feasibility of human MHC class I molecule-restricted SARS-CoV2 epitope peptide cocktail vaccines, thus will facilitate the development of T cell epitope vaccines and specific cellular function detection kits.Competing Interest StatementThe authors have declared no competing interest.}, URL = {https://www.biorxiv.org/content/early/2021/04/01/2021.04.01.438020}, eprint = {https://www.biorxiv.org/content/early/2021/04/01/2021.04.01.438020.full.pdf}, journal = {bioRxiv} }