Unbiased Screens Show CD8+ T Cells of COVID-19 Patients Recognize Shared Epitopes in SARS-CoV-2 that Largely Reside outside the Spike Protein
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Abstract
Developing effective strategies to prevent or treat coronavirus disease 2019 (COVID-19) requires understanding the natural immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We used an unbiased, genome-wide screening technology to determine the precise peptide sequences in SARS-CoV-2 that are recognized by the memory CD8+ T cells of COVID-19 patients. In total, we identified 3-8 epitopes for each of the 6 most prevalent human leukocyte antigen (HLA) types. These epitopes were broadly shared across patients and located in regions of the virus that are not subject to mutational variation. Notably, only 3 of the 29 shared epitopes were located in the spike protein, whereas most epitopes were located in ORF1ab or the nucleocapsid protein. We also found that CD8+ T cells generally do not cross-react with epitopes in the four seasonal coronaviruses that cause the common cold. Overall, these findings can inform development of next-generation vaccines that better recapitulate natural CD8+ T cell immunity to SARS-CoV-2.
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T cell responses against SARS-CoV-2 are highly multi-antigenic and multi-specific, with tens of different epitopes recognized by CD4+ and CD8+ T cells in a given individual.
“the T cell responses against SARS-CoV-2 are highly multi-antigenic and multi-specific, with tens of different epitopes recognized by CD4+ and CD8+ T cells in a given individual.”
From Impact of SARS-CoV-2 variants on the total CD4+ and CD8+ T cell reactivity in infected or vaccinated individuals (2021) · cites this paper as [60]
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- Authors
- Ferretti, A. P., Kula, T., Wang, Y., Nguyen, D. M. V., Weinheimer, A., Dunlap, G. S., Xu, Q., Nabilsi, N., Perullo, C. R., Cristofaro, A. W., Whitton, H. J., Virbasius, A., Olivier, K. J., Buckner, L. R., Alistar, A. T., Whitman, E. D., Bertino, S. A., Chattopadhyay, S., & MacBeath, G.
- Affiliations
- TScan Therapeutics (United States) (US)
- Ochsner Medical Center (US)
- Atlantic Health System (US)
- Corresponding author
- MacBeath, Gavin
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2020-11
- Volume
- 53
- Issue
- 5
- Pages
- 1095-1107.e3
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC7574860
- OpenAlex
- W3093824751
- Cited by
- 318
- References
- 41
- Citations by year
- 2026: 10 · 2025: 19 · 2024: 37 · 2023: 57 · 2022: 85 · 2021: 99 · 2020: 11
- FWCI
- 20.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- medRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- TScan
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- COVID-19 pandemic, SARS-CoV-2, CD8+ T cells, T cell epitopes, shared epitope, HLA types, spike protein, ORF1ab, nucleocapsid protein, vaccine design, natural immune response
- MeSH terms
- Betacoronavirus, COVID-19, SARS-CoV-2, Coronavirus Nucleocapsid Proteins, Adult, Aged, Convalescence, Female, Humans, Immunologic Memory, Male, Middle Aged, Phosphoproteins, Pneumonia, Viral, Viral Proteins, Immunodominant Epitopes, Coronavirus, Coronavirus Infections, CD8-Positive T-Lymphocytes, Epitope Mapping, Epitopes, T-Lymphocyte, Nucleocapsid Proteins, Polyproteins, Young Adult, Pandemics, Spike Glycoprotein, Coronavirus
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