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bioRxiv DOI:10.1101/2020.10.02.324145

SARS-CoV-2 infected cells present HLA-I peptides from canonical and out-of-frame ORFs.

Publication TypeJournal Article
Year of Publication2020
AuthorsWeingarten-Gabbay, S, Klaeger, S, Sarkizova, S, Pearlman, LR, Chen, D-Y, Bauer, MR, Taylor, HB, Conway, HL, Tomkins-Tinch, CH, Finkel, Y, Nachshon, A, Gentili, M, Rivera, KD, Keskin, DB, Rice, CM, Clauser, KR, Hacohen, N, Carr, SA, Abelin, JG, Saeed, M, Sabeti, PC
Date Published2020 Oct 02

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.


Alternate JournalbioRxiv
PubMed ID33024965
PubMed Central IDPMC7536868