ArticleCell2021
Profiling SARS-CoV-2 HLA-I peptidome reveals T cell epitopes from out-of-frame ORFs.
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Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers, 2 of them syntheses that pooled it.
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99citing papers in PubMed, 2 pooled it
11.3field-weighted citation impact, top 1% of its field
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Who cites it
99 citing papers in PubMed, 2 syntheses or guidelines pooled it, 165 citations in OpenAlex.
- A systemic review of T-cell epitopes defined from the proteome of SARS-CoV-2.Virus research · 2023Pooled it
- Genome-scale metabolic modeling reveals SARS-CoV-2-induced metabolic changes and antiviral targets.Molecular systems biology · 2021Pooled it
- IFNλ4 Gene Variants Are Associated with CD8Biomolecules · 2026Article
- Analysis of MHC class II-bound CyHV-2 peptides inJournal of virology · 2026Article
- HLA-E-restricted SARS-CoV-2 epitopes drive CD8Journal of translational medicine · 2026Article
- The race between viral immune evasion and the MHC class I antigen processing pathway.FEMS microbiology reviews · 2026Review
- Article
- Pre-existing and early cellular immune factors correlate with functionally complete protection against primary controlled human SARS-CoV-2 infection.Nature communications · 2025Article
- Decoding the Cryptic Proteome Between Antigens and Novel Functional Proteins.European journal of immunology · 2025Review
- Specific Instability of HLA-A*03:01 Expression in HEK-293 Cells.International journal of molecular sciences · 2025Article
- Targeting infection-specific peptides in immunopeptidomics studies for vaccine target discovery.The Journal of experimental medicine · 2025Article
- Molecular basis of potent antiviral HLA-C-restricted CD8Nature communications · 2025Article
- A pan-cancer atlas of therapeutic T cell targets.bioRxiv : the preprint server for biology · 2025Article
- Pan-viral ORFs discovery using massively parallel ribosome profiling.Science (New York, N.Y.) · 2025Article
- Polymerised superparamagnetic antigen presenting cell lymphocyte capture for enriching tumour reactive T-cells and neoantigen identification.Nature communications · 2025Article
- A Primer on Proteomic Characterization of Intercellular Communication in a Virus Microenvironment.Molecular & cellular proteomics : MCP · 2025Review
- Unveiling conserved HIV-1 open reading frames encoding T cell antigens using ribosome profiling.Nature communications · 2025Article
- Developing T Cell Epitope-Based Vaccines Against Infection: Challenging but Worthwhile.Vaccines · 2025Review
- Development of a Peptide-Based Multiepitope Vaccine from the SARS-CoV-2 Spike Protein for Targeted Immune Response Against COVID-19.Protein and peptide letters · 2025Article
- Translation of bi-directional transcripts enhances MHC-I peptide diversity.Frontiers in immunology · 2025Article
39 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
41 authors at 11 institutions in 2 countries.
Shira Weingarten-GabbayBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address: shirawg@broadinstitute.org.
Susan KlaegerBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: sklaeger@broadinstitute.org.
Siranush SarkizovaBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Leah R PearlmanBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Da-Yuan ChenDepartment of Biochemistry, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
Kathleen M E GallagherCellular Immunotherapy Program and Cancer Center, Massachusetts General Hospital, Charlestown, MA 02129, USA; Harvard Medical School, Boston, MA 02115, USA.
Matthew R BauerBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA.
Hannah B TaylorBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
W Augustine DunnRepertoire Immune Medicines, Cambridge, MA 02139, USA.
Christina TarrRepertoire Immune Medicines, Cambridge, MA 02139, USA.
John SidneyCenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.
Suzanna RachimiBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Hasahn L ConwayDepartment of Biochemistry, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
Katelin KatsisCellular Immunotherapy Program and Cancer Center, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Yuntong WangRepertoire Immune Medicines, Cambridge, MA 02139, USA.
Del Leistritz-EdwardsRepertoire Immune Medicines, Cambridge, MA 02139, USA.
Melissa R DurkinRepertoire Immune Medicines, Cambridge, MA 02139, USA.
Christopher H Tomkins-TinchBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.
Yaara FinkelDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Aharon NachshonDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Matteo GentiliBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Keith D RiveraBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Isabel P CarulliTranslational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA, USA.
Vipheaviny A CheaTranslational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA, USA.
Abishek ChandrashekarCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Cansu Cimen BozkusDepartment of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, USA.
Mary CarringtonRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA; Basic Science Program, Frederick National Laboratory for Cancer Research in the Laboratory of Integrative Cancer Immunology, National Cancer Institute, Bethesda, MD, USA.
MGH COVID-19 Collection & Processing TeamMassachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA.
Nina BhardwajDepartment of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, USA.
Dan H BarouchHarvard Medical School, Boston, MA 02115, USA; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA; Massachusetts Consortium on Pathogen Readiness, Boston, MA, USA.
Alessandro SetteCenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA 92037, USA.
Marcela V MausCellular Immunotherapy Program and Cancer Center, Massachusetts General Hospital, Charlestown, MA 02129, USA; Harvard Medical School, Boston, MA 02115, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
Charles M RiceLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
Karl R ClauserBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Derin B KeskinBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA, USA; Health Informatics Lab, Metropolitan College, Boston University, Boston, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Daniel C PregibonRepertoire Immune Medicines, Cambridge, MA 02139, USA.
Nir HacohenBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
Steven A CarrBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Jennifer G AbelinBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Mohsan SaeedDepartment of Biochemistry, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA. Electronic address: msaeed1@bu.edu.
Pardis C SabetiBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Massachusetts Consortium on Pathogen Readiness, Boston, MA, USA; Department of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Broad Institute · USBoston University · USBeth Israel Deaconess Medical Center · USDana-Farber Cancer Institute · USLa Jolla Institute for Immunology · USMount Sinai Hospital · USRockefeller University · USWeizmann Institute of Science · ILHarvard University · USMassachusetts General Hospital · USRagon Institute of MGH, MIT and Harvard · US
Funding
Viral Genomics: evolution, spread, and host interactionsU19AI110818 · NIAID · BROAD INSTITUTE, INC. · PI CUOMO, CHRISTINA A · 2014 to 2024
$66.5MVirology CoreU19AI082630 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 2009 to 2026
$48.1MTraining Program in Bioinformatics and Integrative GenomicsT32HG002295 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Peter J Park · 2001 to 2026
$15.8MMICROSCALED PROTEOGENOMICS FOR CANCER CLINICAL TRIALSU01CA214125 · NCI · BAYLOR COLLEGE OF MEDICINE · PI ANURAG, MEENAKSHI, CARR, STEVEN A · 2017 to 2021
$7.0MCenter of Excellence for High Throughput Proteogenomic CharacterizationU24CA210986 · NCI · BROAD INSTITUTE, INC. · PI CARR, STEVEN A, GILLETTE, MICHAEL A · 2016 to 2020
$6.4MType I interferon-stimulated genes and the antiviral immune responseR01AI091707 · NIAID · ROCKEFELLER UNIVERSITY · PI RICE, CHARLES M · 2011 to 2020
$5.5MIntegrated high throughput proteogenomic data analysis center for CPTACU24CA210979 · NCI · BROAD INSTITUTE, INC. · PI BIRGER, CHET, GETZ, GAD A · 2016 to 2020
$4.4MMerkel cell polyomavirus HLA class I epitopes for generating therapeutic T cell-based cancer immunotherapyR01CA279391 · NCI · DANA-FARBER CANCER INST · PI Derin B Keskin · 2024 to 2026
$2.2MHost genetic resistance to COVID-19ZIABC011949 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI CARRINGTON, MARY N. · 2020 to 2025
$997kPhysical detection of HLA-C binding peptides to identify and predict immunogenic personal neoepitopes for improving cancer vaccinesR21CA216772 · NCI · DANA-FARBER CANCER INST · PI KESKIN, DERIN B · 2018 to 2019
$420kCCR NIH HHS HHSN261200800001CNCI NIH HHS HHSN261200800001ENCI NIH HHS R01 CA279391NCI NIH HHS R21 CA216772NCI NIH HHS U01 CA214125NCI NIH HHS U24 CA210979NCI NIH HHS U24 CA210986NHGRI NIH HHS T32 HG002295NIAID NIH HHS R01 AI091707NIAID NIH HHS U19 AI082630NIAID NIH HHS U19 AI110818
Abstract
T cell-mediated immunity plays an important role in controlling SARS-CoV-2 infection, but the repertoire of naturally processed and presented viral epitopes on class I human leukocyte antigen (HLA-I) remains uncharacterized. Here, we report the first HLA-I immunopeptidome of SARS-CoV-2 in two cell lines at different times post infection using mass spectrometry. We found HLA-I peptides derived not only from canonical open reading frames (ORFs) but also from internal out-of-frame ORFs in spike and nucleocapsid not captured by current vaccines. Some peptides from out-of-frame ORFs elicited T cell responses in a humanized mouse model and individuals with COVID-19 that exceeded responses to canonical peptides, including some of the strongest epitopes reported to date. Whole-proteome analysis of infected cells revealed that early expressed viral proteins contribute more to HLA-I presentation and immunogenicity. These biological insights, as well as the discovery of out-of-frame ORF epitopes, will facilitate selection of peptides for immune monitoring and vaccine development.
Indexed as
A549 CellsAllelesAmino Acid SequenceAnimalsAntigen PresentationCOVID-19Epitopes, T-LymphocyteFemaleHEK293 CellsHistocompatibility Antigens Class IHumansKineticsMaleMiceOpen Reading FramesPeptidesEpitopes, T-LymphocyteHistocompatibility Antigens Class IPeptidesProteomecoronavirusHLA Class Iimmunogenicityout-of-frame ORF immunopeptidomicsSARS-CoV-2T Cell responseviral infection
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