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dc.contributor.authorBecerra-Artiles, Aniuska
dc.contributor.authorNanaware, Padma P
dc.contributor.authorMuneeruddin, Khaja
dc.contributor.authorWeaver, Grant
dc.contributor.authorShaffer, Scott A
dc.contributor.authorCalvo-Calle, J Mauricio
dc.contributor.authorStern, Lawrence J
dc.date.accessioned2023-09-29T20:37:41Z
dc.date.available2023-09-29T20:37:41Z
dc.date.issued2023-07-27
dc.identifier.citationBecerra-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.en_US
dc.identifier.eissn1553-7374
dc.identifier.doi10.1371/journal.ppat.1011032en_US
dc.identifier.pmid37498934
dc.identifier.urihttp://hdl.handle.net/20.500.14038/52581
dc.description.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.en_US
dc.description.sponsorshipThis 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.en_US
dc.language.isoenen_US
dc.relationThis article is based on a previously available preprint in bioRxiv, https://doi.org/10.1101/2022.12.01.518643en_US
dc.relation.ispartofPLOS Pathogensen_US
dc.relation.urlhttps://doi.org/10.1371/journal.ppat.1011032en_US
dc.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.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectseasonal human coronavirusesen_US
dc.subjectT cell responseen_US
dc.subjectSARS-CoV-2en_US
dc.subjectUMCCTS fundingen_US
dc.titleImmunopeptidome profiling of human coronavirus OC43-infected cells identifies CD4 T-cell epitopes specific to seasonal coronaviruses or cross-reactive with SARS-CoV-2en_US
dc.typeJournal Articleen_US
dc.source.journaltitlePLoS pathogens
dc.source.volume19
dc.source.issue7
dc.source.beginpagee1011032
dc.source.endpage
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.identifier.journalPLoS pathogens
refterms.dateFOA2023-09-29T20:37:42Z
dc.contributor.departmentBiochemistry and Molecular Biotechnologyen_US
dc.contributor.departmentMorningside Graduate School of Biomedical Sciencesen_US
dc.contributor.departmentPathologyen_US
dc.contributor.studentGrant Weaver
dc.description.thesisprogramImmunology and Microbiology


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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.
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.