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SARS-CoV-2-Seronegative Subjects Target CTL Epitopes in the SARS-CoV-2 Nucleoprotein Cross-Reactive to Common Cold Coronaviruses.
Schmidt, Katja G; Nganou-Makamdop, Krystelle; Tenbusch, Matthias; El Kenz, Boutaina; Maier, Clara; Lapuente, Dennis; Überla, Klaus; Spriewald, Bernd; Bergmann, Silke; Harrer, Ellen G; Harrer, Thomas.
  • Schmidt KG; Infectious Disease and Immunodeficiency Section, Department of Internal Medicine 3, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
  • Nganou-Makamdop K; Institute of Clinical and Molecular Virology, Universitätsklinikum Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
  • Tenbusch M; Institute of Clinical and Molecular Virology, Universitätsklinikum Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
  • El Kenz B; Infectious Disease and Immunodeficiency Section, Department of Internal Medicine 3, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
  • Maier C; Institute of Clinical and Molecular Virology, Universitätsklinikum Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
  • Lapuente D; Institute of Clinical and Molecular Virology, Universitätsklinikum Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
  • Überla K; Institute of Clinical and Molecular Virology, Universitätsklinikum Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
  • Spriewald B; Institute of Clinical and Molecular Virology, Universitätsklinikum Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
  • Bergmann S; Department of Medicine 5, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
  • Harrer EG; Infectious Disease and Immunodeficiency Section, Department of Internal Medicine 3, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
  • Harrer T; Infectious Disease and Immunodeficiency Section, Department of Internal Medicine 3, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
Front Immunol ; 12: 627568, 2021.
Article in English | MEDLINE | ID: covidwho-1231335
Semantic information from SemMedBD (by NLM)
1. Epitopes PART_OF Cytotoxic T-Lymphocytes
Subject
Epitopes
Predicate
PART_OF
Object
Cytotoxic T-Lymphocytes
2. Nucleoproteins PART_OF 2019 novel coronavirus
Subject
Nucleoproteins
Predicate
PART_OF
Object
2019 novel coronavirus
3. Epitopes COEXISTS_WITH Nucleoproteins
Subject
Epitopes
Predicate
COEXISTS_WITH
Object
Nucleoproteins
4. Severe disease PROCESS_OF Elderly (population group)
Subject
Severe disease
Predicate
PROCESS_OF
Object
Elderly (population group)
5. risk factors PROCESS_OF Elderly (population group)
Subject
risk factors
Predicate
PROCESS_OF
Object
Elderly (population group)
6. Peptides TREATS OC43
Subject
Peptides
Predicate
TREATS
Object
OC43
7. Human immunodeficiency virus I infection PREDISPOSES COVID-19
Subject
Human immunodeficiency virus I infection
Predicate
PREDISPOSES
Object
COVID-19
8. OC43 LOCATION_OF Epitopes
Subject
OC43
Predicate
LOCATION_OF
Object
Epitopes
9. Cross Reactions PROCESS_OF T-Lymphocyte
Subject
Cross Reactions
Predicate
PROCESS_OF
Object
T-Lymphocyte
10. Alleles AFFECTS COVID-19
Subject
Alleles
Predicate
AFFECTS
Object
COVID-19
11. Epitopes PART_OF Cytotoxic T-Lymphocytes
Subject
Epitopes
Predicate
PART_OF
Object
Cytotoxic T-Lymphocytes
12. Nucleoproteins PART_OF 2019 novel coronavirus
Subject
Nucleoproteins
Predicate
PART_OF
Object
2019 novel coronavirus
13. Epitopes COEXISTS_WITH Nucleoproteins
Subject
Epitopes
Predicate
COEXISTS_WITH
Object
Nucleoproteins
14. Severe disease PROCESS_OF Elderly (population group)
Subject
Severe disease
Predicate
PROCESS_OF
Object
Elderly (population group)
15. risk factors PROCESS_OF Elderly (population group)
Subject
risk factors
Predicate
PROCESS_OF
Object
Elderly (population group)
16. Peptides TREATS OC43
Subject
Peptides
Predicate
TREATS
Object
OC43
17. Human immunodeficiency virus I infection PREDISPOSES COVID-19
Subject
Human immunodeficiency virus I infection
Predicate
PREDISPOSES
Object
COVID-19
18. OC43 LOCATION_OF Epitopes
Subject
OC43
Predicate
LOCATION_OF
Object
Epitopes
19. Cross Reactions PROCESS_OF T-Lymphocyte
Subject
Cross Reactions
Predicate
PROCESS_OF
Object
T-Lymphocyte
20. Alleles AFFECTS COVID-19
Subject
Alleles
Predicate
AFFECTS
Object
COVID-19
ABSTRACT
The beta-coronavirus SARS-CoV-2 induces severe disease (COVID-19) mainly in elderly persons with risk factors, whereas the majority of patients experience a mild course of infection. As the circulating common cold coronaviruses OC43 and HKU1 share some homologous sequences with SARS-CoV-2, beta-coronavirus cross-reactive T-cell responses could influence the susceptibility to SARS-CoV-2 infection and the course of COVID-19. To investigate the role of beta-coronavirus cross-reactive T-cells, we analyzed the T-cell response against a 15 amino acid long peptide (SCoV-DP15 DLSPRWYFYYLGTGP) from the SARS-CoV-2 nucleoprotein sequence with a high homology to the corresponding sequence (QLLPRWYFYYLGTGP) in OC43 and HKU1. SCoV-DP15-specific T-cells were detected in 4 out of 23 (17.4%) SARS-CoV-2-seronegative healthy donors. As HIV-1 infection is a potential risk factor for COVID-19, we also studied a cohort of HIV-1-infected patients on antiretroviral therapy. 44 out of these 116 HIV-1-infected patients (37.9%) showed a specific recognition of the SCoV-DP15 peptide or of shorter peptides within SCoV-DP15 by CD4+ T-cells and/or by CD8+ T-cells. We could define several new cross-reactive HLA-I-restricted epitopes in the SARS-CoV-2 nucleoprotein such as SPRWYFYYL (HLA-B*07, HLA-B*35), DLSPRWYFYY (HLA-A*02), LSPRWYFYY (HLA-A*29), WYFYYLGTGP and WYFYYLGT. Epitope specific CD8+ T-cell lines recognized corresponding epitopes within OC43 and HKU1 to a similar degree or even at lower peptide concentrations suggesting that they were induced by infection with OC43 or HKU1. Our results confirm that SARS-CoV-2-seronegative subjects can target SARS-CoV-2 not only by beta-coronavirus cross-reactive CD4+ T-cells but also by cross-reactive CD8+ cytotoxic T-cells (CTL). The delineation of cross-reactive T-cell epitopes contributes to an efficient epitope-specific immunomonitoring of SARS-CoV-2-specific T-cells. Further prospective studies are needed to prove a protective role of cross-reactive T-cells and their restricting HLA alleles for control of SARS-CoV-2 infection. The frequent observation of SARS-CoV-2-reactive T-cells in HIV-1-infected subjects could be a reason that treated HIV-1 infection does not seem to be a strong risk factor for the development of severe COVID-19.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: T-Lymphocytes, Cytotoxic / CD4-Positive T-Lymphocytes / Common Cold / Epitopes, T-Lymphocyte / SARS-CoV-2 / COVID-19 / Nucleoproteins Type of study: Observational study / Randomized controlled trials / Risk factors Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: Front Immunol Year: 2021 Document Type: Article Affiliation country: Fimmu.2021.627568

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Full text: Available Collection: International databases Database: MEDLINE Main subject: T-Lymphocytes, Cytotoxic / CD4-Positive T-Lymphocytes / Common Cold / Epitopes, T-Lymphocyte / SARS-CoV-2 / COVID-19 / Nucleoproteins Type of study: Observational study / Randomized controlled trials / Risk factors Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: Front Immunol Year: 2021 Document Type: Article Affiliation country: Fimmu.2021.627568