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CD8+ T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope display high naive precursor frequency and TCR promiscuity.
Nguyen, Thi H O; Rowntree, Louise C; Petersen, Jan; Chua, Brendon Y; Hensen, Luca; Kedzierski, Lukasz; van de Sandt, Carolien E; Chaurasia, Priyanka; Tan, Hyon-Xhi; Habel, Jennifer R; Zhang, Wuji; Allen, Lilith F; Earnest, Linda; Mak, Kai Yan; Juno, Jennifer A; Wragg, Kathleen; Mordant, Francesca L; Amanat, Fatima; Krammer, Florian; Mifsud, Nicole A; Doolan, Denise L; Flanagan, Katie L; Sonda, Sabrina; Kaur, Jasveen; Wakim, Linda M; Westall, Glen P; James, Fiona; Mouhtouris, Effie; Gordon, Claire L; Holmes, Natasha E; Smibert, Olivia C; Trubiano, Jason A; Cheng, Allen C; Harcourt, Peter; Clifton, Patrick; Crawford, Jeremy Chase; Thomas, Paul G; Wheatley, Adam K; Kent, Stephen J; Rossjohn, Jamie; Torresi, Joseph; Kedzierska, Katherine.
  • Nguyen THO; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Rowntree LC; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Petersen J; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, VIC 3800, Australia.
  • Chua BY; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia; Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo 060-0808, J
  • Hensen L; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Kedzierski L; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia; Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Melbourne, VIC 3000, Australia.
  • van de Sandt CE; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam 1066CX, the Netherlands.
  • Chaurasia P; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
  • Tan HX; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Habel JR; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Zhang W; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Allen LF; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Earnest L; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Mak KY; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Juno JA; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Wragg K; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Mordant FL; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Amanat F; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Krammer F; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Mifsud NA; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
  • Doolan DL; Centre for Molecular Therapeutics, Australian Institute of Tropical Health & Medicine, James Cook University, Cairns, QLD 4870, Australia.
  • Flanagan KL; School of Health Sciences and School of Medicine, University of Tasmania, Launceston, TAS 7248, Australia; Department of Immunology and Pathology, Monash University, Commercial Road, Melbourne, VIC 3004, Australia; School of Health and Biomedical Science, RMIT University, Melbourne, VIC 3000, Austra
  • Sonda S; School of Health Sciences and School of Medicine, University of Tasmania, Launceston, TAS 7248, Australia.
  • Kaur J; School of Health Sciences and School of Medicine, University of Tasmania, Launceston, TAS 7248, Australia; Tasmanian Vaccine Trial Centre, Clifford Craig Foundation, Launceston General Hospital, Launceston, TAS 7250, Australia.
  • Wakim LM; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Westall GP; Lung Transplant Unit, Alfred Hospital, Melbourne, VIC 3004, Australia.
  • James F; Department of Infectious Diseases, Austin Hospital, Heidelberg, VIC 3084, Australia.
  • Mouhtouris E; Department of Infectious Diseases, Austin Hospital, Heidelberg, VIC 3084, Australia.
  • Gordon CL; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia; Department of Infectious Diseases, Austin Hospital, Heidelberg, VIC 3084, Australia.
  • Holmes NE; Department of Infectious Diseases, Austin Hospital, Heidelberg, VIC 3084, Australia; Department of Medicine and Radiology, The University of Melbourne, Parkville, VIC 3000, Australia; Data Analytics Research and Evaluation (DARE) Centre, Austin Health and The University of Melbourne, Heidelberg, VIC
  • Smibert OC; Department of Infectious Diseases, Austin Hospital, Heidelberg, VIC 3084, Australia; Department of Infectious Diseases, Peter McCallum Cancer Centre, Melbourne, VIC 3000, Australia; The National Centre for Infections in Cancer, Peter McCallum Cancer Centre, Melbourne, VIC 3000, Australia.
  • Trubiano JA; Department of Infectious Diseases, Peter McCallum Cancer Centre, Melbourne, VIC 3000, Australia; The National Centre for Infections in Cancer, Peter McCallum Cancer Centre, Melbourne, VIC 3000, Australia; Centre for Antibiotic Allergy and Research, Department of Infectious Diseases Austin Health, He
  • Cheng AC; Infection Prevention and Healthcare Epidemiology Unit, Alfred Health, Melbourne, VIC 3004, Australia; School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC 3004, Australia.
  • Harcourt P; AFL House, Melbourne, VIC 3001, Australia.
  • Clifton P; AFL House, Melbourne, VIC 3001, Australia.
  • Crawford JC; Department of Immunology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Thomas PG; Department of Immunology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Wheatley AK; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Melbourne, VIC 3000, Australia.
  • Kent SJ; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Melbourne, VIC 3000, Australia; Melbourne Sexual He
  • Rossjohn J; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, VIC 3800, Australia; Ins
  • Torresi J; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Kedzierska K; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia; Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo 060-0808, J
Immunity ; 54(5): 1066-1082.e5, 2021 05 11.
Article in English | MEDLINE | ID: covidwho-1216346
Semantic information from SemMedBD (by NLM)
1. Epitopes PART_OF 2019 novel coronavirus
Subject
Epitopes
Predicate
PART_OF
Object
2019 novel coronavirus
2. COVID-19 PROCESS_OF Patients
Subject
COVID-19
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Patients
3. Cross Reactions NEG_PROCESS_OF Adult
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Cross Reactions
Predicate
NEG_PROCESS_OF
Object
Adult
4. Cross Reactions NEG_PROCESS_OF Elderly (population group)
Subject
Cross Reactions
Predicate
NEG_PROCESS_OF
Object
Elderly (population group)
5. Cross Reactions NEG_PROCESS_OF Child
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Cross Reactions
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NEG_PROCESS_OF
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Child
6. Epitopes PART_OF 2019 novel coronavirus
Subject
Epitopes
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PART_OF
Object
2019 novel coronavirus
7. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
8. Cross Reactions NEG_PROCESS_OF Adult
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Cross Reactions
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NEG_PROCESS_OF
Object
Adult
9. Cross Reactions NEG_PROCESS_OF Elderly (population group)
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Cross Reactions
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NEG_PROCESS_OF
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Elderly (population group)
10. Cross Reactions NEG_PROCESS_OF Child
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Child
ABSTRACT
To better understand primary and recall T cell responses during coronavirus disease 2019 (COVID-19), it is important to examine unmanipulated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells. By using peptide-human leukocyte antigen (HLA) tetramers for direct ex vivo analysis, we characterized CD8+ T cells specific for SARS-CoV-2 epitopes in COVID-19 patients and unexposed individuals. Unlike CD8+ T cells directed toward subdominant epitopes (B7/N257, A2/S269, and A24/S1,208) CD8+ T cells specific for the immunodominant B7/N105 epitope were detected at high frequencies in pre-pandemic samples and at increased frequencies during acute COVID-19 and convalescence. SARS-CoV-2-specific CD8+ T cells in pre-pandemic samples from children, adults, and elderly individuals predominantly displayed a naive phenotype, indicating a lack of previous cross-reactive exposures. T cell receptor (TCR) analyses revealed diverse TCRαß repertoires and promiscuous αß-TCR pairing within B7/N105+CD8+ T cells. Our study demonstrates high naive precursor frequency and TCRαß diversity within immunodominant B7/N105-specific CD8+ T cells and provides insight into SARS-CoV-2-specific T cell origins and subsequent responses.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Receptors, Antigen, T-Cell / Immunodominant Epitopes / CD8-Positive T-Lymphocytes / Coronavirus Nucleocapsid Proteins / SARS-CoV-2 / COVID-19 Type of study: Randomized controlled trials Limits: Adult / Aged / Child / Female / Humans / Male / Middle aged Language: English Journal: Immunity Journal subject: Allergy and Immunology Year: 2021 Document Type: Article Affiliation country: J.immuni.2021.04.009

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Receptors, Antigen, T-Cell / Immunodominant Epitopes / CD8-Positive T-Lymphocytes / Coronavirus Nucleocapsid Proteins / SARS-CoV-2 / COVID-19 Type of study: Randomized controlled trials Limits: Adult / Aged / Child / Female / Humans / Male / Middle aged Language: English Journal: Immunity Journal subject: Allergy and Immunology Year: 2021 Document Type: Article Affiliation country: J.immuni.2021.04.009