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
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/135719
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/135719
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 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 Técnicas2025-09-29T09:57:39Zoai: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:34982025-09-29 09:57:39.542CONICET 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.
publishDate 2021
dc.date.none.fl_str_mv 2021-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv 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
url 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
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1126/sciimmunol.abf7550
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Association for the Advancement of Science
publisher.none.fl_str_mv American Association for the Advancement of Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.069144

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