Identification of HLA-A2 restricted CD8+ T cell epitopes in SARS-CoV-2 structural proteins

Abstract

The outbreak of coronavirus disease 2019 (COVID-19) has now become a pandemic, and the etiologic agent is the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). T cell mediated immune responses play an important role in virus controlling; however, the understanding of the viral protein immunogenicity and the mechanisms of the induced responses are still limited. So, identification of specific epitopes and exploring their immunogenic properties would provide valuable information. In our study, we utilized the Immune Epitope Database and Analysis Resource and NetMHCpan to predict HLA-A2 restricted CD8⁺ T cell epitopes in structural proteins of SARS-CoV-2, and screened out 23 potential epitopes. Among them, 18 peptides showed strong or moderate binding with HLA-A2 with a T2A2 cell binding model. Next, the mixed peptides induced the increased expression of CD69 and highly expressed levels of IFN-γ and granzyme B in CD8⁺ T cells, indicating effective activation of specific CD8⁺ T cells. In addition, the peptide-activated CD8⁺ T cells showed significantly increased killing to the target cells. Furthermore, tetramer staining revealed that the activated CD8⁺ T cells mainly recognized seven epitopes. All together, we identified specific CD8⁺ T cell epitopes in SARS-CoV-2 structural proteins, which could induce the production of specific immune competent CD8⁺ T cells. Our work contributes to the understanding of specific immune responses and vaccine development for SARS-CoV-2.

Keywords: CD8+ T cells; SARS-CoV-2; epitope; structural protein.