Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans
Open accessAbstract
Preexisting immune response to SARS-CoV-2: Robust T cell responses to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus occur in most individuals with coronavirus disease 2019 (COVID-19). Several studies have reported that some people who have not been exposed to SARS-CoV-2 have preexisting reactivity to SARS-CoV-2 sequences. The immunological mechanisms underlying this preexisting reactivity are not clear, but previous exposure to widely circulating common cold coronaviruses might be involved. Mateus et al. found that the preexisting reactivity against SARS-CoV-2 comes from memory T cells and that cross-reactive T cells can specifically recognize a SARS-CoV-2 epitope as well as the homologous epitope from a common cold coronavirus. These findings underline the importance of determining the impacts of preexisting immune memory in COVID-19 disease severity. Science , this issue p. 89
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This cross-reactivity largely originates from previous exposure to circulating common cold coronaviruses.
“This cross-reactivity largely originates from previous exposure to circulating common cold coronaviruses [110-116].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [116]
The section ‘Identification of SARS-CoV-2 epitopes cross-reactive with other common HCoVs’ demonstrates that memory CD4+ T cells recognizing common cold coronaviruses can also recognize SARS-CoV-2 epitopes. But cross-reactivity was detected in 10 of 42 tested T-cell lines; the paper does not establish that previous exposure to those coronaviruses accounts for most of the cross-reactivity overall. (LLM, conf=0.86)
Experimental — accuracy not yet measuredLymphocytes from 20% to 50% of unexposed donors display significant reactivity to SARS-CoV-2 Ag peptide pools.
“lymphocytes from 20% to 50% of unexposed donors display significant reactivity to SARS-CoV-2 Ag peptide pools (Figure 6).”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [116]
Detection of cross-reactive T cells via the AIM assay was previously described.
“Detection of cross-reactive T cells via the AIM assay was previously described (7, 11, 72).”
From SARS-CoV-2 variants of concern partially escape humoral but not T cell responses in COVID-19 convalescent donors and vaccine recipients (2021) · cites this paper as [72]
SARS-CoV-2-reactive T cells from unexposed individuals were reactive to other human coronaviruses.
“One study utilized cell sorting experiments to show that the SARS-CoV-2-reactive T cells identified from SARS-CoV-2 unexposed individuals were primarily from the memory T cell compartment, and they were also reactive to other human coronaviruses144.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [144]
In unexposed individuals, SARS-CoV-2-reactive T cells identified by cell sorting were primarily from the memory T cell compartment.
“One study utilized cell sorting experiments to show that the SARS-CoV-2-reactive T cells identified from SARS-CoV-2 unexposed individuals were primarily from the memory T cell compartment, and they were also reactive to other human coronaviruses144.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [144]
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- Authors
- Mateus, J., Grifoni, A., Tarke, A., Sidney, J., Ramirez, S. I., Dan, J. M., Burger, Z. C., Rawlings, S. A., Smith, D. M., Phillips, E., Mallal, S., Lammers, M., Rubiro, P., Quiambao, L., Sutherland, A., Yu, E. D., da Silva Antunes, R., Greenbaum, J., Frazier, A., Markmann, A. J., Premkumar, L., de Silva, A., Peters, B., Crotty, S., Sette, A., & Weiskopf, D.
- Affiliations
- Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
- La Jolla Institute for Immunology (US)
- University of California San Diego (US)
- Murdoch University (AU)
- University of North Carolina at Chapel Hill (US)
- Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
- Corresponding author
- Sette, Alessandro
- Weiskopf, Daniela
- ORCID
- Mateus, Jose
- Grifoni, Alba
- Tarke, Alison
- Sidney, John
- Ramirez, Sydney I.
- Dan, Jennifer M.
- Burger, Zoe C.
- Rawlings, Stephen A.
- Smith, Davey M.
- Phillips, Elizabeth
- Mallal, Simon
- Lammers, Marshall
- Rubiro, Paul
- Quiambao, Lorenzo
- Sutherland, Aaron
- Yu, Esther Dawen
- da Silva Antunes, Ricardo
- Greenbaum, Jason
- Frazier, April
- Markmann, Alena J.
- Premkumar, Lakshmanane
- de Silva, Aravinda
- Peters, Bjoern
- Crotty, Shane
- Sette, Alessandro
- Weiskopf, Daniela
- Venue
- Science
- Published
- 2020-10-02
- Volume
- 370
- Issue
- 6512
- Pages
- 89-94
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC7574914
- OpenAlex
- W3047159181
- Cited by
- 1,120
- References
- 52
- Citations by year
- 2026: 38 · 2025: 59 · 2024: 95 · 2023: 142 · 2022: 246 · 2021: 393 · 2020: 146 · 2014: 1
- FWCI
- 30.43
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Science (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Murdoch University Research Portal (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (75N9301900065, U19 AI118626, AI142742, AI135078)
- National Institute of Allergy and Infectious Diseases (AI036214)
- University of California, San Diego (AI007036, AI007384)
- 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 epitopes, pre-existing immunity, cross-reactive T cells, memory T cells, common cold coronaviruses, COVID-19 severity
- MeSH terms
- Betacoronavirus, COVID-19, SARS-CoV-2, Blood Donors, Cross Reactions, Humans, Immunologic Memory, Pneumonia, Viral, CD4-Positive T-Lymphocytes, Open Reading Frames, Genome, Viral, Sequence Homology, Coronavirus Infections, Epitope Mapping, Epitopes, T-Lymphocyte, Pandemics
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