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https://ahro.austin.org.au/austinjspui/handle/1/26416| Title: | CD8+ T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope display high naive precursor frequency and TCR promiscuity. | Austin Authors: | 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 L ;Mouhtouris, Effie ;Gordon, Claire L ;Holmes, Natasha E ;Smibert, Olivia C ;Trubiano, Jason ;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 | Affiliation: | Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA Medicine (University of Melbourne) 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 ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Melbourne, VIC 3000, Australia Melbourne Sexual Health Centre, Infectious Diseases Department, Alfred Health, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo 060-0808, Japan Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA Department of Immunology, St Jude Children's Research Hospital, Memphis, TN 38105, USA Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam 1066CX, the Netherlands Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, United Kingdom.. Centre for Molecular Therapeutics, Australian Institute of Tropical Health & Medicine, James Cook University, Cairns, QLD 4870, Australia Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia AFL House, Melbourne, VIC 3001, Australia Lung Transplant Unit, Alfred Hospital, Melbourne, VIC 3004, Australia 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 Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, VIC 3800, Australia Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Melbourne, VIC 3000, 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, Australia Department of Medicine and Radiology, The University of Melbourne, Parkville, VIC 3000, Australia Data Analytics Research and Evaluation (DARE) Centre 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 Infectious Diseases |
Issue Date: | 15-Apr-2021 | Date: | 2021-04-15 | Publication information: | Immunity 2021; online first: 11 May | 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 TCRαβ repertoires and promiscuous αβ-TCR pairing within B7/N105+CD8+ T cells. Our study demonstrates high naive precursor frequency and TCRαβ diversity within immunodominant B7/N105-specific CD8+ T cells and provides insight into SARS-CoV-2-specific T cell origins and subsequent responses. | URI: | https://ahro.austin.org.au/austinjspui/handle/1/26416 | DOI: | 10.1016/j.immuni.2021.04.009 | Journal: | Immunity | PubMed URL: | 33951417 | Type: | Journal Article | Subjects: | COVID-19 SARS-CoV-2-specific CD8+ T cells TCR immunodominant |
| Appears in Collections: | Journal articles |
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