CD8+ T Cell Epitope Variations Suggest a Potential Antigen Presentation Deficiency for Spike Protein of SARS-CoV-2

COVID-19 is caused by a newly identified coronavirus, SARS-CoV-2, and has become a pandemic around the world. The illustration of the immune responses against SARS-CoV-2 is urgently needed for understanding the pathogenesis of the disease and its vaccine development. CD8+ T cells are critical for virus clearance and induce long lasting protection in the host. Here we identified specific HLA-A2 restricted T cell epitopes in the spike protein of SARS-CoV-2. Seven epitope peptides were confirmed to bind with HLA-A2 and potentially be presented by antigen presenting cells to induce host immune responses. Tetramers containing these peptides could interact with specific CD8+ T cells from convalescent COVID-19 patients, and three dominant epitopes were defined. Furthermore, those epitopes could activate and generate epitope-specific T cells in vitro . All these epitopes exhibited high frequency of variations. The epitope variations not only significantly reduced their binding to the HLA-A2 but also decrease the proportion of specific T cell activation, which might contribute to the immune escape of SAR-CoV-2.Funding: This work was supported by grants from the National Key Research and Development Program of China (2018YFC2002003), the Natural Science Foundation of China (U1801285, 81971301), Guangzhou Planned Project of Science and Technology (201904010111, 202002020039), Zhuhai Planned Project of Science and Technology (ZH22036302200067PWC) and the Initial Supporting Foundation of Jinan University.Conflict of Interest: The epitopes and tetramers from this study are the subject of a patent application. No other conflicts exist.Ethical Approval: The Institutional Review Board of the Affiliated Huaqiao Hospital of Jinan University approved this study.