PMID- 34166618 OWN - NLM STAT- MEDLINE DCOM- 20210712 LR - 20231107 IS - 2211-1247 (Electronic) VI - 35 IP - 13 DP - 2021 Jun 29 TI - Identification of presented SARS-CoV-2 HLA class I and HLA class II peptides using HLA peptidomics. PG - 109305 LID - S2211-1247(21)00681-1 [pii] LID - 10.1016/j.celrep.2021.109305 [doi] LID - 109305 AB - 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. CI - Copyright (c) 2021 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Nagler, Adi AU - Nagler A AD - Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. FAU - Kalaora, Shelly AU - Kalaora S AD - Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. FAU - Barbolin, Chaya AU - Barbolin C AD - Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. FAU - Gangaev, Anastasia AU - Gangaev A AD - Division of Molecular Oncology and Immunology, the Netherlands Cancer Institute, the Netherlands. FAU - Ketelaars, Steven L C AU - Ketelaars SLC AD - Division of Molecular Oncology and Immunology, the Netherlands Cancer Institute, the Netherlands. FAU - Alon, Michal AU - Alon M AD - Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. FAU - Pai, Joy AU - Pai J AD - Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. FAU - Benedek, Gil AU - Benedek G AD - Tissue Typing and Immunogenetics Unit, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, Israel. FAU - Yahalom-Ronen, Yfat AU - Yahalom-Ronen Y AD - Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel. FAU - Erez, Noam AU - Erez N AD - Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel. FAU - Greenberg, Polina AU - Greenberg P AD - Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. FAU - Yagel, Gal AU - Yagel G AD - Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. FAU - Peri, Aviyah AU - Peri A AD - Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. FAU - Levin, Yishai AU - Levin Y AD - The de Botton Institute for Protein Profiling, The Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel. FAU - Satpathy, Ansuman T AU - Satpathy AT AD - Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. FAU - Bar-Haim, Erez AU - Bar-Haim E AD - Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel. FAU - Paran, Nir AU - Paran N AD - Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel. FAU - Kvistborg, Pia AU - Kvistborg P AD - Tissue Typing and Immunogenetics Unit, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, Israel. FAU - Samuels, Yardena AU - Samuels Y AD - Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. Electronic address: yardena.samuels@weizmann.ac.il. LA - eng GR - T32 AI007290/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210608 PL - United States TA - Cell Rep JT - Cell reports JID - 101573691 RN - 0 (Antigens, Viral) RN - 0 (COVID-19 Vaccines) RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Peptides) RN - 0 (Peptidomimetics) SB - IM MH - Antigen Presentation MH - Antigens, Viral/*immunology/metabolism MH - COVID-19/*immunology/*virology MH - COVID-19 Vaccines MH - Cell Line MH - Epitopes, T-Lymphocyte/immunology MH - HEK293 Cells MH - Histocompatibility Antigens Class I/immunology MH - Histocompatibility Antigens Class II/immunology MH - Humans MH - Peptides/*immunology MH - Peptidomimetics MH - SARS-CoV-2/genetics/*immunology MH - T-Lymphocytes PMC - PMC8185308 OTO - NOTNLM OT - HLA OT - Peptides OT - Peptidomics OT - SARS-CoV-2 OT - immuno-reactive OT - out-of-frame-ORFs COIS- Declaration of interests Patent applications have been filed on SARS-CoV-2 peptides (Y.S., A.N., and S.K.). The remaining authors declare no competing interests. EDAT- 2021/06/25 06:00 MHDA- 2021/07/13 06:00 PMCR- 2021/06/08 CRDT- 2021/06/24 20:08 PHST- 2020/11/03 00:00 [received] PHST- 2021/01/17 00:00 [revised] PHST- 2021/06/03 00:00 [accepted] PHST- 2021/06/25 06:00 [pubmed] PHST- 2021/07/13 06:00 [medline] PHST- 2021/06/24 20:08 [entrez] PHST- 2021/06/08 00:00 [pmc-release] AID - S2211-1247(21)00681-1 [pii] AID - 109305 [pii] AID - 10.1016/j.celrep.2021.109305 [doi] PST - ppublish SO - Cell Rep. 2021 Jun 29;35(13):109305. doi: 10.1016/j.celrep.2021.109305. Epub 2021 Jun 8.