PMID- 33024965 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230407 DP - 2020 Oct 26 TI - SARS-CoV-2 infected cells present HLA-I peptides from canonical and out-of-frame ORFs. LID - 2020.10.02.324145 [pii] LID - 10.1101/2020.10.02.324145 [doi] AB - T cell-mediated immunity may play a critical role in controlling and establishing protective immunity against SARS-CoV-2 infection; yet the repertoire of viral epitopes responsible for T cell response activation remains mostly unknown. Identification of viral peptides presented on class I human leukocyte antigen (HLA-I) can reveal epitopes for recognition by cytotoxic T cells and potential incorporation into vaccines. Here, we report the first HLA-I immunopeptidome of SARS-CoV-2 in two human cell lines at different times post-infection using mass spectrometry. We found HLA-I peptides derived not only from canonical ORFs, but also from internal out-of-frame ORFs in Spike and Nucleoprotein not captured by current vaccines. Proteomics analyses of infected cells revealed that SARS-CoV-2 may interfere with antigen processing and immune signaling pathways. Based on the endogenously processed and presented viral peptides that we identified, we estimate that a pool of 24 peptides would provide one or more peptides for presentation by at least one HLA allele in 99% of the human population. These biological insights and the list of naturally presented SARS-CoV-2 peptides will facilitate data-driven selection of peptides for immune monitoring and vaccine development. FAU - Weingarten-Gabbay, Shira AU - Weingarten-Gabbay S AUID- ORCID: 0000-0001-7579-0236 FAU - Klaeger, Susan AU - Klaeger S AUID- ORCID: 0000-0002-0074-5163 FAU - Sarkizova, Siranush AU - Sarkizova S AUID- ORCID: 0000-0003-2530-8610 FAU - Pearlman, Leah R AU - Pearlman LR FAU - Chen, Da-Yuan AU - Chen DY FAU - Bauer, Matthew R AU - Bauer MR FAU - Taylor, Hannah B AU - Taylor HB FAU - Conway, Hasahn L AU - Conway HL FAU - Tomkins-Tinch, Christopher H AU - Tomkins-Tinch CH FAU - Finkel, Yaara AU - Finkel Y AUID- ORCID: 0000-0002-3843-2357 FAU - Nachshon, Aharon AU - Nachshon A AUID- ORCID: 0000-0003-2283-5220 FAU - Gentili, Matteo AU - Gentili M FAU - Rivera, Keith D AU - Rivera KD FAU - Keskin, Derin B AU - Keskin DB AUID- ORCID: 0000-0002-8496-6181 FAU - Rice, Charles M AU - Rice CM FAU - Clauser, Karl R AU - Clauser KR AUID- ORCID: 0000-0002-1052-9456 FAU - Hacohen, Nir AU - Hacohen N AUID- ORCID: 0000-0002-2349-2656 FAU - Carr, Steven A AU - Carr SA AUID- ORCID: 0000-0002-7203-4299 FAU - Abelin, Jennifer G AU - Abelin JG AUID- ORCID: 0000-0001-5262-7241 FAU - Saeed, Mohsan AU - Saeed M AUID- ORCID: 0000-0002-9843-1890 FAU - Sabeti, Pardis C AU - Sabeti PC LA - eng GR - U24 CA210986/CA/NCI NIH HHS/United States GR - T32 HG002295/HG/NHGRI NIH HHS/United States GR - U24 CA270823/CA/NCI NIH HHS/United States GR - U24 CA210979/CA/NCI NIH HHS/United States GR - U01 CA214125/CA/NCI NIH HHS/United States PT - Preprint DEP - 20201026 PL - United States TA - bioRxiv JT - bioRxiv : the preprint server for biology JID - 101680187 PMC - PMC7536868 EDAT- 2020/10/08 06:00 MHDA- 2020/10/08 06:01 PMCR- 2020/11/09 CRDT- 2020/10/07 05:52 PHST- 2020/10/08 06:00 [pubmed] PHST- 2020/10/08 06:01 [medline] PHST- 2020/10/07 05:52 [entrez] PHST- 2020/11/09 00:00 [pmc-release] AID - 2020.10.02.324145 [pii] AID - 10.1101/2020.10.02.324145 [doi] PST - epublish SO - bioRxiv [Preprint]. 2020 Oct 26:2020.10.02.324145. doi: 10.1101/2020.10.02.324145.