Immunopeptidome profiling of human coronavirus OC43-infected cells identifies CD4 T-cell epitopes specific to seasonal coronaviruses or cross-reactive with SARS-CoV-2
Nanaware, Padma P
Shaffer, Scott A
Calvo-Calle, J Mauricio
Stern, Lawrence J
Student AuthorsGrant Weaver
Academic ProgramImmunology and Microbiology
UMass Chan AffiliationsBiochemistry and Molecular Biotechnology
Morningside Graduate School of Biomedical Sciences
Document TypeJournal Article
MetadataShow full item record
AbstractSeasonal "common-cold" human coronaviruses are widely spread throughout the world and are mainly associated with mild upper respiratory tract infections. The emergence of highly pathogenic coronaviruses MERS-CoV, SARS-CoV, and most recently SARS-CoV-2 has prompted increased attention to coronavirus biology and immunopathology, but the T-cell response to seasonal coronaviruses remains largely uncharacterized. Here we report the repertoire of viral peptides that are naturally processed and presented upon infection of a model cell line with seasonal coronavirus OC43. We identified MHC-bound peptides derived from each of the viral structural proteins (spike, nucleoprotein, hemagglutinin-esterase, membrane, and envelope) as well as non-structural proteins nsp3, nsp5, nsp6, and nsp12. Eighty MHC-II bound peptides corresponding to 14 distinct OC43-derived epitopes were identified, including many at very high abundance within the overall MHC-II peptidome. Fewer and less abundant MHC-I bound OC43-derived peptides were observed, possibly due to MHC-I downregulation induced by OC43 infection. The MHC-II peptides elicited low-abundance recall T-cell responses in most donors tested. In vitro assays confirmed that the peptides were recognized by CD4+ T cells and identified the presenting HLA alleles. T-cell responses cross-reactive between OC43, SARS-CoV-2, and the other seasonal coronaviruses were confirmed in samples of peripheral blood and peptide-expanded T-cell lines. Among the validated epitopes, spike protein S903-917 presented by DPA1*01:03/DPB1*04:01 and S1085-1099 presented by DRB1*15:01 shared substantial homology to other human coronaviruses, including SARS-CoV-2, and were targeted by cross-reactive CD4 T cells. Nucleoprotein N54-68 and hemagglutinin-esterase HE128-142 presented by DRB1*15:01 and HE259-273 presented by DPA1*01:03/DPB1*04:01 are immunodominant epitopes with low coronavirus homology that are not cross-reactive with SARS-CoV-2. Overall, the set of naturally processed and presented OC43 epitopes comprise both OC43-specific and human coronavirus cross-reactive epitopes, which can be used to follow CD4 T-cell cross-reactivity after infection or vaccination, and to guide selection of epitopes for inclusion in pan-coronavirus vaccines.
SourceBecerra-Artiles A, Nanaware PP, Muneeruddin K, Weaver GC, Shaffer SA, Calvo-Calle JM, Stern LJ. Immunopeptidome profiling of human coronavirus OC43-infected cells identifies CD4 T-cell epitopes specific to seasonal coronaviruses or cross-reactive with SARS-CoV-2. PLoS Pathog. 2023 Jul 27;19(7):e1011032. doi: 10.1371/journal.ppat.1011032. PMID: 37498934; PMCID: PMC10409285.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/52581
Funding and AcknowledgementsThis work was supported by grants from NIH (R01-AI13798, UL1-TR001453), the UMass Medical School COVID-19 Pandemic Research Fund, and the UMass Chan Flow Cytometry Facility Shared Equipment Grant (S10 OD034358). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Related ResourcesThis article is based on a previously available preprint in bioRxiv, https://doi.org/10.1101/2022.12.01.518643
RightsCopyright: © 2023 Becerra-Artiles et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Except where otherwise noted, this item's license is described as Copyright: © 2023 Becerra-Artiles et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.