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Journal article
Identification of presented SARS-CoV-2 HLA class I and HLA class II peptides using HLA peptidomics
Cell reports (Cambridge), Vol.35(13), 109305
29/Jun/2021
Abstract
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 presented viral antigens. Using HLA peptidomics, we are able to identify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-derived peptides presented by highly prevalent HLA class I (HLA-I) molecules by using infected cells as well as overexpression of SARS-CoV-2 genes. We find 26 HLA-I peptides and 36 HLA class II (HLA-II) peptides. Among the identified peptides, some are shared between different cells and some are derived from out-of-frame open reading frames (ORFs). Seven of these peptides were previously shown to be immunogenic, and we identify two additional immunoreactive peptides by using HLA multimer staining. These results may aid the development of the next generation of SARS-CoV-2 vaccines based on presented viral-specific antigens that span several of the viral genes. [Display omitted] HLA peptidomics enable the identification of SARS-CoV-2-derived HLA peptides•SARS-CoV-2 peptides can be derived from canonical and non-canonical ORFs•Shared SARS-CoV-2 peptides are identified in different cell types•Several SARS-CoV-2 peptides are immunogenic Using HLA peptidomics, Nagler et al. identify SARS-CoV-2-derived peptides presented by highly prevalent HLA-I and HLA-II. Identified peptides are derived from various canonical and non-canonical viral ORFs, are shared between different cells, and are immunogenic. As the identified peptides are unique to SARS-CoV-2, they could potentially serve as future treatment targets.
Details
- Title
- Identification of presented SARS-CoV-2 HLA class I and HLA class II peptides using HLA peptidomics
- Creators
- Adi Nagler - 972WIS_INST___122Shelly Kalaora - 972WIS_INST___122Chaya Barbolin - 972WIS_INST___122Anastasia Gangaev - 972WIS_INST___7946c6d9-d8f5-4ce1-926c-300fa9199d1eSteven L.C Ketelaars - 972WIS_INST___7946c6d9-d8f5-4ce1-926c-300fa9199d1eMichal Alon - 972WIS_INST___122Joy Pai - Stanford University School of MedicineGil Benedek - Hebrew University of JerusalemYfat Yahalom-Ronen - Israel Institute for Biological ResearchNoam Erez - Israel Institute for Biological ResearchPolina Greenberg - 972WIS_INST___122Gal Yagel - Weizmann Institute of ScienceAviyah Peri - 972WIS_INST___122Yishai Levin - 972WIS_INST___890Ansuman T Satpathy - Stanford University School of MedicineErez Bar-Haim - Israel Institute for Biological ResearchNir Paran - Israel Institute for Biological ResearchPia Kvistborg - 972WIS_INST___7946c6d9-d8f5-4ce1-926c-300fa9199d1eYardena Samuels - 972WIS_INST___122
- Resource Type
- Journal article
- Publication Details
- Cell reports (Cambridge), Vol.35(13), 109305; 29/Jun/2021
- Number of pages
- 19
- Publisher
- Elsevier Inc
- Language
- English
- DOI
- https://doi.org/10.1016/j.celrep.2021.109305
- Grants
- Grant note
- We thank Prof. Nevan J. Krogan and Dr. David E. Gordon for providing SARS-CoV-2 envelope, nuclocapsid, nonstructural protein-6 and membrane pLVX-EF1alpha-IRES-Puro plasmids. We thank Prof. Moshe Kotler for his advice regarding viral pathogenesis. We thank Tali Wiesel for the graphical scheme. We thank Dr. Tamar Ziv, Shani Ben-lulu, Keren Bendalak and the Smoler Protein Research Center, Technion, Israel for the proteomic analysis of infected cells. This work was funded by the Intramural Research Programs of the National Cancer Institute. Y.S. is supported by the Israel Science Foundation grant No. 696/17, the European Research Council (ERC) under the European Union’s Horizon 2020 Programme for Research and Innovation (grant agreement No. 754282), ERC (CoG-770854), MRA (#622106), Rising Tide Foundation, Henry Chanoch Krenter Institute for Biomedical Imaging and Genomics, Estate of Alice Schwarz-Gardos, Estate of John Hunter, Knell Family, Peter and Patricia Gruber Award, the Hamburger Family, Karl-Johan Persson and Miel de Botton. A.N., S.K., and Y.S. designed the study and wrote the paper. A.N., S.K., and C.B. analyzed the data and performed and supervised the experiments. A.N., S.K., M.A., and P.G. performed the HLA peptidomics experiments. A.N., P.G., G.Y., and A.P. grew the cell lines for HLA peptidomics. Y.L. helped with the HLA peptidomics and mass spectrometry analyses. G.B. performed HLA typing. Y.Y.-R., N.E., E.B.-H., and N.P. performed SARS-CoV-2 infection experiments. A.G., S.L.C.K., and P.K. performed T cell reactivity assays. J.P. and A.T.S. helped with analysis. All authors contributed to the final version of the paper.
- Record Identifier
- 993292223803596
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