The landscape of the SARS-CoV-2 HLA-peptidome

The human leukocyte antigen (HLA)-bound-viral antigens, serve as an immunological signature that can be selectively recognized by T cells. As viruses evolve by acquiring mutations, it is essential to identify a range of viral presented antigens. Utilizing HLA-peptidomics we Identified SARS-CoV-2-derived peptides presented by highly prevalent HLA Class-I (HLA-I) molecules using infected cells as well as overexpression of SARS-CoV-2 genes. We found 26 HLA-I peptides and 36 HLA class-II (HLA-II) peptides, which are estimated to be presented by at least one HLA allele in 99% of the world population. Among the identified peptides were recurrently presented HLA-I peptides, peptides derived from out-of-frame-ORFs and presentation-hotspots. Seven of these peptides were previously shown to be immunogenic, and we identified two novel immuno-reactive peptides using HLA-multimer staining. These results may aid the development of the next generation of SARS-CoV-2 vaccines based on viral-specific-presented antigens that span several of the viral genes.