Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19
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Abstract
The development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and therapeutics will depend on understanding viral immunity. We studied T cell memory in 42 patients following recovery from COVID-19 (28 with mild disease and 14 with severe disease) and 16 unexposed donors, using interferon-γ-based assays with peptides spanning SARS-CoV-2 except ORF1. The breadth and magnitude of T cell responses were significantly higher in severe as compared with mild cases. Total and spike-specific T cell responses correlated with spike-specific antibody responses. We identified 41 peptides containing CD4+ and/or CD8+ epitopes, including six immunodominant regions. Six optimized CD8+ epitopes were defined, with peptide-MHC pentamer-positive cells displaying the central and effector memory phenotype. In mild cases, higher proportions of SARS-CoV-2-specific CD8+ T cells were observed. The identification of T cell responses associated with milder disease will support an understanding of protective immunity and highlights the potential of including non-spike proteins within future COVID-19 vaccine design.
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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 [120]
The Results (Identification of SARS-CoV-2-specific T cell peptides containing epitopes; page unavailable) identify CD4+ and CD8+ responses in people who had recovered from COVID-19, including mild cases. The Methods (Synthetic peptides; Two-dimensional peptide matrix system; pages unavailable) describe overlapping peptides arranged in matrix pools, not HLA class I- and II-predicted peptide megapools. This paper does not establish the claim for patients with acute COVID-19. (LLM, conf=0.88)
Experimental — accuracy not yet measuredVAERD has generally not occurred when a Th1-biased CD4+ response, marked by increased IFNγ, IL-2, and TNF, is induced.
“By contrast, VAERD has not usually occurred if a TH1 cell-biased CD4+ T cell response is elicited, reflected by increased levels of interferon-γ (IFNγ), IL-2 and tumour necrosis factor (TNF)44–46,49.”
From Immunological mechanisms of vaccine-induced protection against COVID-19 in humans (2021) · cites this paper as [46]
Robust CD4+ and CD8+ T cell memory is induced after COVID-19, and multiple COVID-19 vaccines elicit CD4+ and CD8+ T cell responses.
“Robust CD4+ and CD8+ T cell memory is induced after COVID-19,22,39, 40, 41 and multiple COVID-19 vaccines elicit CD4+ and CD8+ T cell responses.26,42, 43, 44, 45”
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 [40]
T cell responses will contribute to control of SARS-CoV-2 infection, particularly in re-infected convalescent patients.
“It should be noted that all plasma and sera tested completely inhibited entry at the lowest dilution tested and that T cell responses will contribute to control of SARS-CoV-2 infection, particularly in re-infected convalescent patients (Grifoni et al., 2020; Peng et al., 2020).”
From SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies (2021) · cites this paper as Peng et al., 2020
T cell responses are detected after almost all SARS-CoV-2 infections.
“T cell responses are detected after almost all SARS-CoV-2 infections (Grifoni et al., 2020; Rydyznski Moderbacher et al., 2020; Peng et al., 2020; Sekine et al., 2020).”
From Adaptive immunity to SARS-CoV-2 and COVID-19 (2021) · cites this paper as Peng et al., 2020
The presence of virus-specific CD8+ T cells is associated with better COVID-19 outcomes.
“In SARS-CoV-2 infections, the presence of virus-specific CD8+ T cells has been associated with better COVID-19 outcomes (Rydyznski Moderbacher et al., 2020; Peng et al., 2020).”
From Adaptive immunity to SARS-CoV-2 and COVID-19 (2021) · cites this paper as Peng et al., 2020
Current evidence suggests that an early, robust and diverse T cell response against SARS-CoV-2 correlates with milder COVID-19 outcomes.
“Current evidence suggests an early, robust, and diverse T cell response directed against SARS-CoV-2 correlates with milder COVID-19 outcomes126,131,132”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [132]
Severe COVID-19 is associated with reduced TCR diversity against SARS-CoV-2 epitopes.
“Severe COVID-19 has been associated with lower TCR diversity against SARS-CoV-2 epitopes131,132.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [132]
For CD8+ T cells, some studies report diminished cytotoxicity and cytokine production in severe COVID-19.
“For CD8+ T cells, there are reports of diminished CD8+ cytotoxicity and cytokine production in severe cases126,132, while others report the opposite141, and still others find no differences142.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [132]
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- Authors
- Peng, Y., Mentzer, A. J., Liu, G., Yao, X., Yin, Z., Dong, D., Dejnirattisai, W., Rostron, T., Supasa, P., Liu, C., López-Camacho, C., Slon-Campos, J., Zhao, Y., Stuart, D. I., Paesen, G. C., Grimes, J. M., Antson, A. A., Bayfield, O. W., Hawkins, D. E. D. P., Ker, D.-S., Wang, B., Turtle, L., Subramaniam, K., Thomson, P., Zhang, P., Dold, C., Ratcliff, J., Simmonds, P., de Silva, T., Sopp, P., Wellington, D., Rajapaksa, U., Chen, Y.-L., Salio, M., Napolitani, G., Paes, W., Borrow, P., Kessler, B. M., Fry, J. W., Schwabe, N. F., Semple, M. G., Baillie, J. K., Moore, S. C., Openshaw, P. J. M., Ansari, M. A., Dunachie, S., Barnes, E., Frater, J., Kerr, G., Goulder, P., Lockett, T., Levin, R., Zhang, Y., Jing, R., Ho, L.-P., Oxford Immunology Network Covid-19 Response T cell Consortium, Barnes, E., Dong, D., Dong, T., Dunachie, S., Frater, J., Goulder, P., Kerr, G., Klenerman, P., Liu, G., McMichael, A., Napolitani, G., Ogg, G., Peng, Y., Salio, M., Yao, X., Yin, Z., ISARIC4C Investigators, Kenneth Baillie, J., Klenerman, P., Mentzer, A. J., Moore, S. C., Openshaw, P. J. M., Semple, M. G., Stuart, D. I., Turtle, L., Cornall, R. J., Conlon, C. P., Klenerman, P., Screaton, G. R., Mongkolsapaya, J., McMichael, A., Knight, J. C., Ogg, G., & Dong, T.
- Affiliations
- University of Oxford (GB)
- Centre for Human Genetics (GB)
- University of York (GB)
- University of Liverpool (GB)
- ProImmune (United Kingdom) (GB)
- Oxford University Hospitals NHS Trust (GB)
- Worthing Hospital (GB)
- Capital Medical University (CN)
- University of Edinburgh (GB)
- Siriraj Hospital (TH)
- ORCID
- Dejnirattisai, Wanwisa
- Supasa, Piyada
- Liu, Chang
- López-Camacho, César
- Slon-Campos, Jose
- Zhao, Yuguang
- Paesen, Guido C.
- Grimes, Jonathan M.
- Antson, Alfred A.
- Bayfield, Oliver W.
- Hawkins, Dorothy E. D. P.
- Ker, De-Sheng
- Wang, Beibei
- Subramaniam, Krishanthi
- Thomson, Paul
- Zhang, Ping
- Dold, Christina
- Ratcliff, Jeremy
- Simmonds, Peter
- Wellington, Dannielle
- Rajapaksa, Ushani
- Chen, Yi-Ling
- Paes, Wayne
- Borrow, Persephone
- Kessler, Benedikt M.
- Fry, Jeremy W.
- Ansari, M. Azim
- Zhang, Yonghong
- Ho, Ling-Pei
- Cornall, Richard J.
- Screaton, Gavin R.
- Mongkolsapaya, Juthathip
- Knight, Julian C.
- Venue
- Nature Immunology
- Published
- 2020-09-04
- Volume
- 21
- Issue
- 11
- Pages
- 1336-1345
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC7611020
- OpenAlex
- W3082438395
- Cited by
- 1,179
- References
- 42
- Citations by year
- 2026: 41 · 2025: 68 · 2024: 118 · 2023: 171 · 2022: 291 · 2021: 398 · 2020: 91
- FWCI
- 30.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Immunology (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Oxford University Research Archive (ORA) (University of Oxford) (acceptedVersion)
- PubMed Central (submittedVersion)
- Funders
- RCUK | Medical Research Council (MC_PC_19059)
- Chinese Academy of Medical Sciences (2018-I2M-2-002)
- China Scholarship Council
- Wellcome Trust (205228/Z/16/Z, 110058/Z/15/Z, 215091/Z/18/Z, 095541/A/11/Z, award 206377 to AAA)
- DH | NIHR | Health Services Research Programme (NIHR200907, CO-CIN-01)
- University of Liverpool
- University of Oxford
- University of Edinburgh
- DH | National Institute for Health Research (NIHR200927 /WHRG_P82523, NIHR201385 / WHRR P84026, NIHR200907)
- Imperial College London (IS-BRC-1215-20013)
- Worthing Hospital
- Oxford University Hospitals NHS Trust
- National Institutes of Health, National Key R&D Program of China
- University of York
- ProImmune Ltd
- Bill and Melinda Gates Foundation (MC_PC_19059)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- SARS-CoV-2, COVID-19 pandemic, T cell memory, CD4+ T cells, CD8+ T cells, epitope mapping, immunodominant epitopes, spike protein, disease severity, convalescent patients, central memory T cells, effector memory T cells, antiviral immunity
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