Comprehensive analysis of T cell immunodominance and immunoprevalence of SARS-CoV-2 epitopes in COVID-19 cases
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Abstract
T cells are involved in control of SARS-CoV-2 infection. To establish the patterns of immunodominance of different SARS-CoV-2 antigens and precisely measure virus-specific CD4 + and CD8 + T cells, we study epitope-specific T cell responses of 99 convalescent coronavirus disease 2019 (COVID-19) cases. The SARS-CoV-2 proteome is probed using 1,925 peptides spanning the entire genome, ensuring an unbiased coverage of human leukocyte antigen (HLA) alleles for class II responses. For HLA class I, we study an additional 5,600 predicted binding epitopes for 28 prominent HLA class I alleles, accounting for wide global coverage. We identify several hundred HLA-restricted SARS-CoV-2-derived epitopes. Distinct patterns of immunodominance are observed, which differ for CD4 + T cells, CD8 + T cells, and antibodies. The class I and class II epitopes are combined into epitope megapools to facilitate identification and quantification of SARS-CoV-2-specific CD4 + and CD8 + T cells.
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Using HLA class I and II predicted peptide megapools, circulating SARS-CoV-2-specific CD8+ and CD4+ T cells were identified in COVID-19 acute, mild and convalescent patients.
“Using HLA class I and II predicted peptide “megapools,” circulating SARS-CoV-2-specific CD8+ and CD4+ T cells were identified in COVID-19 acute, mild and convalescent patients [110, 118-125].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [121]
The Results section, “Reactivity of megapools based on the experimentally identified epitopes” (page unavailable), reports CD4+ and CD8+ T-cell responses to peptide megapools in convalescent COVID-19 donors. It does not report testing acute patients. The “SARS-CoV-2 peptides and epitope screening strategy” section also says class II screening used overlapping peptides rather than HLA class II predictions, so the claim overstates both the patient groups and the prediction method. (LLM, conf=0.89)
Experimental — accuracy not yet measured509 (97.3%) of 523 CD8+ T cell epitopes are totally conserved within the P.1 variant.
“509 (97.3%) within the B.1.351 and P.1 variants”
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 [51]
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 [51]
509 (97.3%) of 523 CD8+ T cell epitopes are totally conserved within the B.1.351 variant.
“509 (97.3%) within the B.1.351 and P.1 variants”
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 [51]
508 (97.1%) of 523 CD8+ T cell epitopes are totally conserved within the B.1.1.7 variant.
“508 (97.1%) of these 523 CD8+ T cell epitopes are totally conserved within the B.1.1.7 variant”
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 [51]
512 (97.9%) of 523 CD8+ T cell epitopes are totally conserved within the CAL.20C variant.
“512 (97.9%) within the CAL.20C variant”
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 [51]
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Bieberich, F., Vazquez-Lombardi, R., Yermanos, A., Ehling, R. A., Mason, D. M., Wagner, B., Kapetanovic, E., Roberto, R. B. D., Weber, C. R., Savic, M., et al. (2021) · bioRxiv · doi:10.3389/fimmu.2021.701085 · Cited by 39 · see citing works
Performance of the T-SPOTⓇ.COVID test for detecting SARS-CoV-2-responsive T cells
Kruse, M., Dark, C., Aspden, M., Cochrane, D., Competiello, R., Peltz, M., Torres, L., Wrighton-Smith, P., & Dudek, M. (2021) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2021.09.073 · Cited by 42 · see citing works
Recruitment of highly cytotoxic CD8+ T cell receptors in mild SARS-CoV-2 infection
Wagner, K. I., Mateyka, L. M., Jarosch, S., Grass, V., Weber, S., Schober, K., Hammel, M., Burrell, T., Kalali, B. N., Poppert, H., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.110214 · Cited by 45 · see citing works
Yang, L., Beek, M. V., Wang, Z., Muecksch, F., Canis, M., Hatziioannou, T., Bieniasz, P. D., Nussenzweig, M. C., & Chakraborty, A. K. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112256 · Cited by 46 · see citing works
The MegaPool Approach to Characterize Adaptive CD4+ and CD8+ T Cell Responses
Antunes, R. D. S., Weiskopf, D., Sidney, J., Rubiro, P., Peters, B., Arlehamn, C. S. L., Grifoni, A., & Sette, A. (2023) · Current Protocols · doi:10.1002/cpz1.934 · Cited by 46 · see citing works
Self-citationGarushyants, S. K., Rogozin, I. B., & Koonin, E. V. (2021) · Communications Biology · doi:10.1038/s42003-021-02858-9 · Cited by 45 · see citing works
- Authors
- Tarke, A., Sidney, J., Kidd, C. K., Dan, J. M., Ramirez, S. I., Yu, E. D., Mateus, J., da Silva Antunes, R., Moore, E., Rubiro, P., Methot, N., Phillips, E., Mallal, S., Frazier, A., Rawlings, S. A., Greenbaum, J. A., Peters, B., Smith, D. M., Crotty, S., Weiskopf, D., Grifoni, A., & Sette, A.
- Affiliations
- La Jolla Institute for Immunology (US)
- Murdoch University (AU)
- University of California San Diego (US)
- Corresponding author
- Grifoni, Alba
- Sette, Alessandro
- ORCID
- Venue
- Cell Reports Medicine
- Publisher
- Elsevier BV
- Published
- 2021-02
- Volume
- 2
- Issue
- 2
- Pages
- 100204
- ISSN
- 2666-3791 (ISSN-L)
- PMC
- PMC7837622
- OpenAlex
- W3122458452
- Cited by
- 540
- References
- 58
- Citations by year
- 2026: 22 · 2025: 41 · 2024: 71 · 2023: 118 · 2022: 156 · 2021: 131 · 2014: 1
- FWCI
- 37.36
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports Medicine (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, other-oa)
- PubMed Central (submittedVersion)
- Murdoch University Research Portal (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- ImmPort
- Funders
- University of California, San Diego (AI007036and AI007384)
- National Institute of Allergy and Infectious Diseases (75N93019C00001, AI42742, 75N9301900065)
- National Institutes of Health (AI036214, U01 CA260541-01, AI135078)
- John and Mary Tu Foundation
- Gilead Sciences
- Università degli Studi di Genova
- 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
- SARS-CoV-2, COVID-19 pandemic, epitope-specific T cell responses, HLA-restricted epitopes, CD4+ T cells, CD8+ T cells, HLA class II, convalescent patients, virus-specific T cells
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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