Profiling MHC-I and MHC-II canonical and out-of-frame epitopes from SARS-CoV-2 and seasonal human coronavirus infected human cells

Abstract Understanding the targets of adaptive immunity to SARS-CoV-2 is essential for vaccine development and interpretation of coronavirus disease 2019 (COVID-19) pathogenesis. SARS-CoV-2 and other human coronaviruses share substantial sequence homology raising the possibility that the previous exposure to seasonal “common cold” human coronaviruses could impact the T cell response upon SARS-CoV-2 infection. Detailed investigation of the antigenic peptides presented in SARS-CoV-2 and other common coronavirus infections would be beneficial to understand the impact of preexisting T cell mediated immunity on SARS-CoV-2 infection. The repertoire of naturally processed and presented viral peptides by MHC II upon SARS-CoV-2 and seasonal human coronaviruses infections remains largely uncharacterized. Here, we report the MHC I and II immunopeptidome of cells infected with SARS-CoV-2 or hCoV-OC43, one of the seasonal coronaviruses. We identified 11 MHC I peptides and 13 MHC II peptides of SARS-CoV-2 infected cells including both canonical and out-of-frame spike epitopes, 27 MHC I and 91 MHC II peptides from membrane, nucleocapsid, spike and hemagglutinin-esterase from OC43 infected cells using mass spectrometry. We validated some peptides using HLA peptide binding assays, and these peptides were shown to recall T cell responses in donors with presumed history of common cold viral infection. Some of these peptides share substantial homology with common cold coronaviruses, indicating possibility of conserved T cell epitopes eliciting the protective immunity in COVID-19. The identification of naturally presented peptides and their striking homology with other coronavirus could aid in the peptide selection for the vaccine development.