{"doi":"10.1101/2020.10.02.324145","title":"SARS-CoV-2 infected cells present HLA-I peptides from canonical and out-of-frame ORFs","abstract":"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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":119381,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9485,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":44968,"name":"Susan Klaeger","orcid":"0000-0002-0074-5163","position":1,"is_corresponding":false},{"id":44969,"name":"Siranush Sarkizova","orcid":"0000-0003-2530-8610","position":2,"is_corresponding":false},{"id":555102,"name":"Leah R. Pearlman","orcid":null,"position":3,"is_corresponding":false},{"id":249892,"name":"Da‐Yuan Chen","orcid":"0000-0002-1957-3330","position":4,"is_corresponding":false},{"id":554217,"name":"Matthew R. Bauer","orcid":"0000-0001-6309-3548","position":5,"is_corresponding":false},{"id":554218,"name":"Hannah Taylor","orcid":"0000-0003-0525-4598","position":6,"is_corresponding":false},{"id":249893,"name":"Hasahn L. Conway","orcid":"0000-0001-7328-3521","position":7,"is_corresponding":false},{"id":472081,"name":"Christopher H. Tomkins-Tinch","orcid":"0000-0002-9114-6421","position":8,"is_corresponding":false},{"id":37910,"name":"Yaara Finkel","orcid":"0000-0002-3843-2357","position":9,"is_corresponding":false},{"id":239718,"name":"Aharon Nachshon","orcid":"0000-0003-2283-5220","position":10,"is_corresponding":false},{"id":28893,"name":"Matteo Gentili","orcid":"0000-0002-6970-8133","position":11,"is_corresponding":false},{"id":442084,"name":"Keith Rivera","orcid":"0000-0003-2979-9576","position":12,"is_corresponding":false},{"id":25296,"name":"Derin B. Keskin","orcid":"0000-0002-8496-6181","position":13,"is_corresponding":false},{"id":104737,"name":"Charles M. Rice","orcid":"0000-0003-3087-8079","position":14,"is_corresponding":false},{"id":2216,"name":"Karl R. Clauser","orcid":"0000-0002-1052-9456","position":15,"is_corresponding":false},{"id":409,"name":"Nir Hacohen","orcid":"0000-0002-2349-2656","position":16,"is_corresponding":false},{"id":2226,"name":"Steven A. Carr","orcid":"0000-0002-7203-4299","position":17,"is_corresponding":false},{"id":554219,"name":"Jennifer G. Abelin","orcid":"0000-0001-5262-7241","position":18,"is_corresponding":false},{"id":232300,"name":"Mohsan Saeed","orcid":"0000-0001-8505-7054","position":19,"is_corresponding":false},{"id":7155,"name":"Pardis C. Sabeti","orcid":"0000-0002-9843-1890","position":20,"is_corresponding":false},{"id":554216,"name":"Shira Weingarten-Gabbay","orcid":"0000-0001-7579-0236","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-18T23:14:08.313144Z","pmid":"33024965","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}