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The HLA-II immunopeptidome of SARS-CoV-2

ABSTRACT: Weingarten-Gabbay S, Chen D, Sarkizova S, Taylor HB, Gentili M, Pearlman LR, Bauer MR, Rice CM, Clauser KR, Hacohen N, Carr SA, Abelin JG, Saeed M, Sabeti PC. 2023. Targeted synthetic vaccines have the potential to transform our response to viral outbreaks; yet the design of these vaccines requires a comprehensive knowledge of viral immunogens, including T-cell epitopes. Having previously mapped the SARS-CoV-2 HLA-I landscape, here we report viral peptides that are naturally processed and loaded onto HLA-II complexes in infected cells. We identified over 500 unique viral peptides from canonical proteins, as well as overlapping internal open reading frames (ORFs), revealing, for the first time, the contribution of internal ORFs to the HLA-II peptide repertoire. Most HLA-II peptides co-localized with the known CD4+ T cell epitopes in COVID-19 patients, including a finding that two reported immunodominant regions in the SARS-CoV-2 membrane protein were formed at the level of HLA-II presentation. We observed that the HLA-I and HLA-II pathways target distinct viral proteins, with the structural proteins accounting for the majority of the HLA-II peptidome and non-structural and non-canonical proteins accounting for the majority of the HLA-I peptidome. These findings suggest that the future vaccines should incorporate multiple viral elements harboring CD4+ and CD8+ T cell epitopes to maximize their effectiveness.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Sars-cov-2 Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Steven A. Carr

PROVIDER: MSV000091943 | MassIVE | Mon May 15 06:02:00 BST 2023

SECONDARY ACCESSION(S): PXD042231

REPOSITORIES: MassIVE

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