SARS-CoV-2–specific CD8+ T cell responses in convalescent COVID-19 individuals
Characterization of the T cell response in individuals who recover from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is critical to understanding its contribution to protective immunity. A multiplexed peptide-MHC tetramer approach was used to screen 408 SARS-CoV-2 candidate...
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| Published in | The Journal of clinical investigation Vol. 131; no. 5; pp. 1 - 13 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
American Society for Clinical Investigation
01.03.2021
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| Subjects | |
| Online Access | Get full text |
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| Abstract | Characterization of the T cell response in individuals who recover from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is critical to understanding its contribution to protective immunity. A multiplexed peptide-MHC tetramer approach was used to screen 408 SARS-CoV-2 candidate epitopes for CD8+ T cell recognition in a cross-sectional sample of 30 coronavirus disease 2019 convalescent individuals. T cells were evaluated using a 28-marker phenotypic panel, and findings were modelled against time from diagnosis and from humoral and inflammatory responses. There were 132 SARS-CoV-2-specific CD8+ T cell responses detected across 6 different HLAs, corresponding to 52 unique epitope reactivities. CD8+ T cell responses were detected in almost all convalescent individuals and were directed against several structural and nonstructural target epitopes from the entire SARS-CoV-2 proteome. A unique phenotype for SARS-CoV-2-specific T cells was observed that was distinct from other common virus-specific T cells detected in the same cross-sectional sample and characterized by early differentiation kinetics. Modelling demonstrated a coordinated and dynamic immune response characterized by a decrease in inflammation, increase in neutralizing antibody titer, and differentiation of a specific CD8+ T cell response. Overall, T cells exhibited distinct differentiation into stem cell and transitional memory states (subsets), which may be key to developing durable protection. |
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| AbstractList | Characterization of the T cell response in individuals who recover from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is critical to understanding its contribution to protective immunity. A multiplexed peptide-MHC tetramer approach was used to screen 408 SARS-CoV-2 candidate epitopes for CD8+ T cell recognition in a cross-sectional sample of 30 coronavirus disease 2019 convalescent individuals. T cells were evaluated using a 28-marker phenotypic panel, and findings were modelled against time from diagnosis and from humoral and inflammatory responses. There were 132 SARS-CoV-2-specific CD8+ T cell responses detected across 6 different HLAs, corresponding to 52 unique epitope reactivities. CD8+ T cell responses were detected in almost all convalescent individuals and were directed against several structural and nonstructural target epitopes from the entire SARS-CoV-2 proteome. A unique phenotype for SARS-CoV-2-specific T cells was observed that was distinct from other common virus-specific T cells detected in the same cross-sectional sample and characterized by early differentiation kinetics. Modelling demonstrated a coordinated and dynamic immune response characterized by a decrease in inflammation, increase in neutralizing antibody titer, and differentiation of a specific CD8+ T cell response. Overall, T cells exhibited distinct differentiation into stem cell and transitional memory states (subsets), which may be key to developing durable protection.Characterization of the T cell response in individuals who recover from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is critical to understanding its contribution to protective immunity. A multiplexed peptide-MHC tetramer approach was used to screen 408 SARS-CoV-2 candidate epitopes for CD8+ T cell recognition in a cross-sectional sample of 30 coronavirus disease 2019 convalescent individuals. T cells were evaluated using a 28-marker phenotypic panel, and findings were modelled against time from diagnosis and from humoral and inflammatory responses. There were 132 SARS-CoV-2-specific CD8+ T cell responses detected across 6 different HLAs, corresponding to 52 unique epitope reactivities. CD8+ T cell responses were detected in almost all convalescent individuals and were directed against several structural and nonstructural target epitopes from the entire SARS-CoV-2 proteome. A unique phenotype for SARS-CoV-2-specific T cells was observed that was distinct from other common virus-specific T cells detected in the same cross-sectional sample and characterized by early differentiation kinetics. Modelling demonstrated a coordinated and dynamic immune response characterized by a decrease in inflammation, increase in neutralizing antibody titer, and differentiation of a specific CD8+ T cell response. Overall, T cells exhibited distinct differentiation into stem cell and transitional memory states (subsets), which may be key to developing durable protection. Characterization of the T cell response in individuals who recover from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is critical to understanding its contribution to protective immunity. A multiplexed peptide-MHC tetramer approach was used to screen 408 SARS-CoV-2 candidate epitopes for CD8+ T cell recognition in a cross-sectional sample of 30 coronavirus disease 2019 convalescent individuals. T cells were evaluated using a 28-marker phenotypic panel, and findings were modelled against time from diagnosis and from humoral and inflammatory responses. There were 132 SARS-CoV-2-specific CD8+ T cell responses detected across 6 different HLAs, corresponding to 52 unique epitope reactivities. CD8+ T cell responses were detected in almost all convalescent individuals and were directed against several structural and nonstructural target epitopes from the entire SARS-CoV-2 proteome. A unique phenotype for SARS-CoV-2-specific T cells was observed that was distinct from other common virus-specific T cells detected in the same cross-sectional sample and characterized by early differentiation kinetics. Modelling demonstrated a coordinated and dynamic immune response characterized by a decrease in inflammation, increase in neutralizing antibody titer, and differentiation of a specific CD8+ T cell response. Overall, T cells exhibited distinct differentiation into stem cell and transitional memory states (subsets), which may be key to developing durable protection. Characterization of the T cell response in individuals who recover from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is critical to understanding its contribution to protective immunity. A multiplexed peptide-MHC tetramer approach was used to screen 408 SARS-CoV-2 candidate epitopes for CD8· T cell recognition in a cross-sectional sample of 30 coronavirus disease 2019 convalescent individuals. T cells were evaluated using a 28-marker phenotypic panel, and findings were modelled against time from diagnosis and from humoral and inflammatory responses. There were 132 SARS-CoV-2-specific CD8· T cell responses detected across 6 different HLAs, corresponding to 52 unique epitope reactivities. CD8· T cell responses were detected in almost all convalescent individuals and were directed against several structural and nonstructural target epitopes from the entire SARS-CoV-2 proteome. A unique phenotype for SARS-CoV-2-specific T cells was observed that was distinct from other common virus-specific T cells detected in the same cross-sectional sample and characterized by early differentiation kinetics. Modelling demonstrated a coordinated and dynamic immune response characterized by a decrease in inflammation, increase in neutralizing antibody titer, and differentiation of a specific CD8· T cell response. Overall, T cells exhibited distinct differentiation into stem cell and transitional memory states (subsets), which may be key to developing durable protection. Characterization of the T cell response in individuals who recover from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is critical to understanding its contribution to protective immunity. A multiplexed peptide-MHC tetramer approach was used to screen 408 SARS-CoV-2 candidate epitopes for CD8 + T cell recognition in a cross-sectional sample of 30 coronavirus disease 2019 convalescent individuals. T cells were evaluated using a 28-marker phenotypic panel, and findings were modelled against time from diagnosis and from humoral and inflammatory responses. There were 132 SARS-CoV-2–specific CD8 + T cell responses detected across 6 different HLAs, corresponding to 52 unique epitope reactivities. CD8 + T cell responses were detected in almost all convalescent individuals and were directed against several structural and nonstructural target epitopes from the entire SARS-CoV-2 proteome. A unique phenotype for SARS-CoV-2–specific T cells was observed that was distinct from other common virus-specific T cells detected in the same cross-sectional sample and characterized by early differentiation kinetics. Modelling demonstrated a coordinated and dynamic immune response characterized by a decrease in inflammation, increase in neutralizing antibody titer, and differentiation of a specific CD8 + T cell response. Overall, T cells exhibited distinct differentiation into stem cell and transitional memory states (subsets), which may be key to developing durable protection. |
| Author | Redd, Andrew D. Shoham, Shmuel Patel, Eshan U. Nardin, Alessandra Tobian, Aaron A.R. Bonny, Tania S. Bettinotti, Maria P. Pekosz, Andrew Casadevall, Arturo Newell, Evan W. Sullivan, David Benner, Sarah E. Sumatoh, Hermi Kared, Hassen Laeyendecker, Oliver Carbajo, Daniel Abel, Brian Littlefield, Kirsten Bloch, Evan M. Quinn, Thomas C. Fehlings, Michael Kairi, Faris |
| AuthorAffiliation | 4 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA 7 Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA 3 Department of Medicine and 1 ImmunoScape, Singapore, Singapore 5 Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA 2 Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA 6 Department of Epidemiology and |
| AuthorAffiliation_xml | – name: 1 ImmunoScape, Singapore, Singapore – name: 5 Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA – name: 3 Department of Medicine and – name: 6 Department of Epidemiology and – name: 2 Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA – name: 4 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA – name: 7 Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA |
| Author_xml | – sequence: 1 givenname: Hassen surname: Kared fullname: Kared, Hassen – sequence: 2 givenname: Andrew D. surname: Redd fullname: Redd, Andrew D. – sequence: 3 givenname: Evan M. orcidid: 0000-0001-8181-9517 surname: Bloch fullname: Bloch, Evan M. – sequence: 4 givenname: Tania S. surname: Bonny fullname: Bonny, Tania S. – sequence: 5 givenname: Hermi surname: Sumatoh fullname: Sumatoh, Hermi – sequence: 6 givenname: Faris surname: Kairi fullname: Kairi, Faris – sequence: 7 givenname: Daniel orcidid: 0000-0001-8779-7697 surname: Carbajo fullname: Carbajo, Daniel – sequence: 8 givenname: Brian surname: Abel fullname: Abel, Brian – sequence: 9 givenname: Evan W. orcidid: 0000-0002-2889-243X surname: Newell fullname: Newell, Evan W. – sequence: 10 givenname: Maria P. surname: Bettinotti fullname: Bettinotti, Maria P. – sequence: 11 givenname: Sarah E. surname: Benner fullname: Benner, Sarah E. – sequence: 12 givenname: Eshan U. orcidid: 0000-0003-2174-5004 surname: Patel fullname: Patel, Eshan U. – sequence: 13 givenname: Kirsten orcidid: 0000-0002-6019-0673 surname: Littlefield fullname: Littlefield, Kirsten – sequence: 14 givenname: Oliver orcidid: 0000-0002-6429-4760 surname: Laeyendecker fullname: Laeyendecker, Oliver – sequence: 15 givenname: Shmuel surname: Shoham fullname: Shoham, Shmuel – sequence: 16 givenname: David orcidid: 0000-0003-0319-0578 surname: Sullivan fullname: Sullivan, David – sequence: 17 givenname: Arturo orcidid: 0000-0002-9402-9167 surname: Casadevall fullname: Casadevall, Arturo – sequence: 18 givenname: Andrew orcidid: 0000-0003-3248-1761 surname: Pekosz fullname: Pekosz, Andrew – sequence: 19 givenname: Alessandra surname: Nardin fullname: Nardin, Alessandra – sequence: 20 givenname: Michael surname: Fehlings fullname: Fehlings, Michael – sequence: 21 givenname: Aaron A.R. surname: Tobian fullname: Tobian, Aaron A.R. – sequence: 22 givenname: Thomas C. orcidid: 0000-0002-0404-1315 surname: Quinn fullname: Quinn, Thomas C. |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33427749$$D View this record in MEDLINE/PubMed |
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| Copyright | Copyright American Society for Clinical Investigation Mar 2021 2021 American Society for Clinical Investigation 2021 American Society for Clinical Investigation |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ObjectType-Undefined-3 Authorship note: HK, ADR, and EMB contributed equally to this work. MF, AART, and TCQ are co–senior authors. |
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| SubjectTerms | Adult Aged Antibodies Antibodies, Neutralizing - immunology Antibodies, Viral - immunology Antigens Biomedical research CD8 antigen CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - pathology Cell differentiation Cell recognition Convalescence Coronaviridae Coronaviruses COVID-19 COVID-19 - immunology COVID-19 - pathology Cytomegalovirus Epitopes Female Genotype & phenotype Histocompatibility antigen HLA HLA Antigens - immunology Humans Infections Inflammation Influenza Lymphocytes Lymphocytes T Major histocompatibility complex Male Memory cells Middle Aged Models, Immunological Pandemics Peptides Phenotypes Proteins Proteomes SARS-CoV-2 - immunology Severe acute respiratory syndrome coronavirus 2 Stem cells Vaccines |
| Title | SARS-CoV-2–specific CD8+ T cell responses in convalescent COVID-19 individuals |
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