The Presentation of SARS-CoV-2 Peptides by the Common HLA-A*02:01 Molecule

CD8+ T cells are crucial for anti-viral immunity, however, understanding T cell responses requires the identification of viral epitopes, and their presentation by Human Leukocyte Antigens (HLA). To date, few SARS-CoV-2-specific CD8+ T cell epitopes have been described. Internal viral proteins, are typically more conserved than surface proteins, and are often the target of CD8+ T cells. Therefore, we have characterised eight peptides derived from the internal SARS-CoV-2 Nucleocapsid protein predicted to bind HLA-A*02:01, the most common HLA molecule in the global population. We determined not all peptides could form a complex with HLA-A*02:01, and the six crystal structures determined revealed that some peptides adopted a mobile conformation. We therefore provide a molecular understanding of SARS-CoV-2 CD8+ T cell epitopes. Furthermore, we show that there is limited pre-existing CD8+ T cell response towards these epitopes in unexposed individuals. Together, these data show that SARS-CoV-2 Nucleocapsid might not contain potent epitopes restricted to HLA-A*02:01. Funding: This work was funded by the Australian National Health and Medical Research Council (NHMRC), C.S. and D.S.M.C. are supported with an AINSE Early Career Research Grant, E.J.G. is supported by an NHMRC CJ Martin Fellowship (#1110429) and S.G. is supported by an NHMRC Senior Research Fellowship (#1159272). Conflict of Interest: The authors have no competing interests. Ethical Approval: All work using human samples was approved by the Monash University Human Ethics Committee (#19079 and #18380).