SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8+ T cell activation in COVID-19 patients
- Autores
- Saini, Sunil Kumar; Hersby, Ditte Stampe; Tamhane, Tripti; Povlsen, Helle Rus; Amaya Hernandez, Susana Patricia; Nielsen, Morten; Gang, Anne Ortved; Hadrup, Sine Reker
- Año de publicación
- 2021
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- T cells are important for effective viral clearance, elimination of virus-infected cells and long-term disease protection. To examine the full-spectrum of CD8+ T cell immunity in COVID-19, we experimentally evaluated 3141 major histocompatibility (MHC) class I-binding peptides covering the complete SARS-CoV-2 genome. Using DNA-barcoded peptide-MHC complex (pMHC) multimers combined with a T cell phenotype panel, we report a comprehensive list of 122 immunogenic and a subset of immunodominant SARS-CoV-2 T cell epitopes. Substantial CD8+ T cell recognition was observed in COVID-19 patients, with up to 27% of all CD8+ lymphocytes interacting with SARS-CoV-2-derived epitopes. Most immunogenic regions were derived from open reading frame (ORF) 1 and ORF3, with ORF1 containing most of the immunodominant epitopes. CD8+ T cell recognition of lower affinity was also observed in healthy donors toward SARS-CoV-2-derived epitopes. This pre-existing T cell recognition signature was partially overlapping with the epitope landscape observed in COVID-19 patients and may drive the further expansion of T cell responses to SARS-CoV-2 infection. Importantly the phenotype of the SARS-CoV-2-specific CD8+ T cells, revealed a strong T cell activation in COVID-19 patients, while minimal T cell activation was seen in healthy individuals. We found that patients with severe disease displayed significantly larger SARS-CoV-2-specific T cell populations compared to patients with mild diseases and these T cells displayed a robust activation profile. These results further our understanding of T cell immunity to SARS-CoV-2 infection and hypothesize that strong antigen-specific T cell responses are associated with different disease outcomes.
Fil: Saini, Sunil Kumar. Technical University of Denmark; Dinamarca
Fil: Hersby, Ditte Stampe. Copenhagen University Hospital; Dinamarca
Fil: Tamhane, Tripti. Technical University of Denmark; Dinamarca
Fil: Povlsen, Helle Rus. Technical University of Denmark; Dinamarca
Fil: Amaya Hernandez, Susana Patricia. Technical University of Denmark; Dinamarca
Fil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Gang, Anne Ortved. Copenhagen University Hospital; Dinamarca
Fil: Hadrup, Sine Reker. Technical University of Denmark; Dinamarca - Materia
-
Sars-Cov-2
Epitopes
T cells
COVID-19 - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/135719
Ver los metadatos del registro completo
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SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8+ T cell activation in COVID-19 patientsSaini, Sunil KumarHersby, Ditte StampeTamhane, TriptiPovlsen, Helle RusAmaya Hernandez, Susana PatriciaNielsen, MortenGang, Anne OrtvedHadrup, Sine RekerSars-Cov-2EpitopesT cellsCOVID-19https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3T cells are important for effective viral clearance, elimination of virus-infected cells and long-term disease protection. To examine the full-spectrum of CD8+ T cell immunity in COVID-19, we experimentally evaluated 3141 major histocompatibility (MHC) class I-binding peptides covering the complete SARS-CoV-2 genome. Using DNA-barcoded peptide-MHC complex (pMHC) multimers combined with a T cell phenotype panel, we report a comprehensive list of 122 immunogenic and a subset of immunodominant SARS-CoV-2 T cell epitopes. Substantial CD8+ T cell recognition was observed in COVID-19 patients, with up to 27% of all CD8+ lymphocytes interacting with SARS-CoV-2-derived epitopes. Most immunogenic regions were derived from open reading frame (ORF) 1 and ORF3, with ORF1 containing most of the immunodominant epitopes. CD8+ T cell recognition of lower affinity was also observed in healthy donors toward SARS-CoV-2-derived epitopes. This pre-existing T cell recognition signature was partially overlapping with the epitope landscape observed in COVID-19 patients and may drive the further expansion of T cell responses to SARS-CoV-2 infection. Importantly the phenotype of the SARS-CoV-2-specific CD8+ T cells, revealed a strong T cell activation in COVID-19 patients, while minimal T cell activation was seen in healthy individuals. We found that patients with severe disease displayed significantly larger SARS-CoV-2-specific T cell populations compared to patients with mild diseases and these T cells displayed a robust activation profile. These results further our understanding of T cell immunity to SARS-CoV-2 infection and hypothesize that strong antigen-specific T cell responses are associated with different disease outcomes.Fil: Saini, Sunil Kumar. Technical University of Denmark; DinamarcaFil: Hersby, Ditte Stampe. Copenhagen University Hospital; DinamarcaFil: Tamhane, Tripti. Technical University of Denmark; DinamarcaFil: Povlsen, Helle Rus. Technical University of Denmark; DinamarcaFil: Amaya Hernandez, Susana Patricia. Technical University of Denmark; DinamarcaFil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Gang, Anne Ortved. Copenhagen University Hospital; DinamarcaFil: Hadrup, Sine Reker. Technical University of Denmark; DinamarcaAmerican Association for the Advancement of Science2021-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/135719Saini, Sunil Kumar; Hersby, Ditte Stampe; Tamhane, Tripti; Povlsen, Helle Rus; Amaya Hernandez, Susana Patricia; et al.; SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8+ T cell activation in COVID-19 patients; American Association for the Advancement of Science; Science Immunology; 6; 58; 4-2021; 1-232470-9468CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1126/sciimmunol.abf7550info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:55:17Zoai:ri.conicet.gov.ar:11336/135719instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:55:17.823CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8+ T cell activation in COVID-19 patients |
| title |
SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8+ T cell activation in COVID-19 patients |
| spellingShingle |
SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8+ T cell activation in COVID-19 patients Saini, Sunil Kumar Sars-Cov-2 Epitopes T cells COVID-19 |
| title_short |
SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8+ T cell activation in COVID-19 patients |
| title_full |
SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8+ T cell activation in COVID-19 patients |
| title_fullStr |
SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8+ T cell activation in COVID-19 patients |
| title_full_unstemmed |
SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8+ T cell activation in COVID-19 patients |
| title_sort |
SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8+ T cell activation in COVID-19 patients |
| dc.creator.none.fl_str_mv |
Saini, Sunil Kumar Hersby, Ditte Stampe Tamhane, Tripti Povlsen, Helle Rus Amaya Hernandez, Susana Patricia Nielsen, Morten Gang, Anne Ortved Hadrup, Sine Reker |
| author |
Saini, Sunil Kumar |
| author_facet |
Saini, Sunil Kumar Hersby, Ditte Stampe Tamhane, Tripti Povlsen, Helle Rus Amaya Hernandez, Susana Patricia Nielsen, Morten Gang, Anne Ortved Hadrup, Sine Reker |
| author_role |
author |
| author2 |
Hersby, Ditte Stampe Tamhane, Tripti Povlsen, Helle Rus Amaya Hernandez, Susana Patricia Nielsen, Morten Gang, Anne Ortved Hadrup, Sine Reker |
| author2_role |
author author author author author author author |
| dc.subject.none.fl_str_mv |
Sars-Cov-2 Epitopes T cells COVID-19 |
| topic |
Sars-Cov-2 Epitopes T cells COVID-19 |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| dc.description.none.fl_txt_mv |
T cells are important for effective viral clearance, elimination of virus-infected cells and long-term disease protection. To examine the full-spectrum of CD8+ T cell immunity in COVID-19, we experimentally evaluated 3141 major histocompatibility (MHC) class I-binding peptides covering the complete SARS-CoV-2 genome. Using DNA-barcoded peptide-MHC complex (pMHC) multimers combined with a T cell phenotype panel, we report a comprehensive list of 122 immunogenic and a subset of immunodominant SARS-CoV-2 T cell epitopes. Substantial CD8+ T cell recognition was observed in COVID-19 patients, with up to 27% of all CD8+ lymphocytes interacting with SARS-CoV-2-derived epitopes. Most immunogenic regions were derived from open reading frame (ORF) 1 and ORF3, with ORF1 containing most of the immunodominant epitopes. CD8+ T cell recognition of lower affinity was also observed in healthy donors toward SARS-CoV-2-derived epitopes. This pre-existing T cell recognition signature was partially overlapping with the epitope landscape observed in COVID-19 patients and may drive the further expansion of T cell responses to SARS-CoV-2 infection. Importantly the phenotype of the SARS-CoV-2-specific CD8+ T cells, revealed a strong T cell activation in COVID-19 patients, while minimal T cell activation was seen in healthy individuals. We found that patients with severe disease displayed significantly larger SARS-CoV-2-specific T cell populations compared to patients with mild diseases and these T cells displayed a robust activation profile. These results further our understanding of T cell immunity to SARS-CoV-2 infection and hypothesize that strong antigen-specific T cell responses are associated with different disease outcomes. Fil: Saini, Sunil Kumar. Technical University of Denmark; Dinamarca Fil: Hersby, Ditte Stampe. Copenhagen University Hospital; Dinamarca Fil: Tamhane, Tripti. Technical University of Denmark; Dinamarca Fil: Povlsen, Helle Rus. Technical University of Denmark; Dinamarca Fil: Amaya Hernandez, Susana Patricia. Technical University of Denmark; Dinamarca Fil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina Fil: Gang, Anne Ortved. Copenhagen University Hospital; Dinamarca Fil: Hadrup, Sine Reker. Technical University of Denmark; Dinamarca |
| description |
T cells are important for effective viral clearance, elimination of virus-infected cells and long-term disease protection. To examine the full-spectrum of CD8+ T cell immunity in COVID-19, we experimentally evaluated 3141 major histocompatibility (MHC) class I-binding peptides covering the complete SARS-CoV-2 genome. Using DNA-barcoded peptide-MHC complex (pMHC) multimers combined with a T cell phenotype panel, we report a comprehensive list of 122 immunogenic and a subset of immunodominant SARS-CoV-2 T cell epitopes. Substantial CD8+ T cell recognition was observed in COVID-19 patients, with up to 27% of all CD8+ lymphocytes interacting with SARS-CoV-2-derived epitopes. Most immunogenic regions were derived from open reading frame (ORF) 1 and ORF3, with ORF1 containing most of the immunodominant epitopes. CD8+ T cell recognition of lower affinity was also observed in healthy donors toward SARS-CoV-2-derived epitopes. This pre-existing T cell recognition signature was partially overlapping with the epitope landscape observed in COVID-19 patients and may drive the further expansion of T cell responses to SARS-CoV-2 infection. Importantly the phenotype of the SARS-CoV-2-specific CD8+ T cells, revealed a strong T cell activation in COVID-19 patients, while minimal T cell activation was seen in healthy individuals. We found that patients with severe disease displayed significantly larger SARS-CoV-2-specific T cell populations compared to patients with mild diseases and these T cells displayed a robust activation profile. These results further our understanding of T cell immunity to SARS-CoV-2 infection and hypothesize that strong antigen-specific T cell responses are associated with different disease outcomes. |
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2021 |
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2021-04 |
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http://hdl.handle.net/11336/135719 Saini, Sunil Kumar; Hersby, Ditte Stampe; Tamhane, Tripti; Povlsen, Helle Rus; Amaya Hernandez, Susana Patricia; et al.; SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8+ T cell activation in COVID-19 patients; American Association for the Advancement of Science; Science Immunology; 6; 58; 4-2021; 1-23 2470-9468 CONICET Digital CONICET |
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http://hdl.handle.net/11336/135719 |
| identifier_str_mv |
Saini, Sunil Kumar; Hersby, Ditte Stampe; Tamhane, Tripti; Povlsen, Helle Rus; Amaya Hernandez, Susana Patricia; et al.; SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8+ T cell activation in COVID-19 patients; American Association for the Advancement of Science; Science Immunology; 6; 58; 4-2021; 1-23 2470-9468 CONICET Digital CONICET |
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eng |
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