Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/35517
Title: SARS-CoV-2-specific CD8+ T cells from people with long COVID establish and maintain effector phenotype and key TCR signatures over 2 years.
Austin Authors: Rowntree, Louise C;Audsley, Jennifer;Allen, Lilith F;McQuilten, Hayley A;Hagen, Ruth R;Chaurasia, Priyanka;Petersen, Jan;Littler, Dene R;Tan, Hyon-Xhi;Murdiyarso, Lydia;Habel, Jennifer R;Foo, Isabelle J H;Zhang, Wuji;Ten Berge, Elizabeth R V;Ganesh, Hanujah;Kaewpreedee, Prathanporn;Lee, Kelly W K;Cheng, Samuel M S;Kwok, Janette S Y;Jayasinghe, Dhilshan;Gras, Stephanie;Juno, Jennifer A;Wheatley, Adam K;Kent, Stephen J;Rossjohn, Jamie;Cheng, Allen C;Kotsimbos, Tom C;Trubiano, Jason ;Holmes, Natasha E ;Pang Chan, Ken Ka;Hui, David S C;Peiris, Malik;Poon, Leo L M;Lewin, Sharon R;Doherty, Peter C;Thevarajan, Irani;Valkenburg, Sophie A;Kedzierska, Katherine;Nguyen, Thi H O
Affiliation: Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
Division of Public Health Laboratory Sciences, School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region, China.
Division of Transplantation and Immunogenetics, Department of Pathology, Queen Mary Hospital, Hong Kong Special Administrative Region, China.
Infection & Immunity Program, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC 3083, Australia.;Department of Biochemistry and Chemistry, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, VIC 3083, Australia.
Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.;Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, United Kingdom.
School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC 3004, Australia.;Monash Infectious Diseases, Monash Health and School of Clinical Sciences, Monash University, Clayton, VIC 3168, Australia.
Department of Respiratory Medicine, The Alfred Hospital, Melbourne, VIC 3004, Australia.;Department of Medicine, Central Clinical School, The Alfred Hospital, Monash University, Melbourne, VIC 3004, Australia.
Department of Infectious Diseases, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.;Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia.;National Centre for Infections in Cancer, Peter McCallum Cancer Centre, Melbourne, VIC 3000, Australia.;Department of Medicine (Austin Health), University of Melbourne, Heidelberg, VIC 3084, Australia.;Centre for Antibiotic Allergy and Research, Department of Infectious Diseases, Austin Health, Heidelberg, VIC 3084, Australia.
Centre for Antibiotic Allergy and Research
Data Analytics Research and Evaluation (DARE) Centre
Infectious Diseases
HKU-Pasteur Research Pole, School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region, China.;Division of Public Health Laboratory Sciences, School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region, China.;Centre for Immunology and Infection, Hong Kong Science and Technology Park, New Territories, Hong Kong Special Administrative Region, China.
Department of Infectious Diseases, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.;Victorian Infectious Diseases Service, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.;Department of Infectious Disease, Alfred Hospital and Monash University, Melbourne, VIC 3000, Australia.
Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
Issue Date: 24-Sep-2024
Date: 2024
Publication information: Proceedings of the National Academy of Sciences of the United States of America 2024-09-24; 121(39)
Abstract: Long COVID occurs in a small but important minority of patients following COVID-19, reducing quality of life and contributing to healthcare burden. Although research into underlying mechanisms is evolving, immunity is understudied. SARS-CoV-2-specific T cell responses are of key importance for viral clearance and COVID-19 recovery. However, in long COVID, the establishment and persistence of SARS-CoV-2-specific T cells are far from clear, especially beyond 12 mo postinfection and postvaccination. We defined ex vivo antigen-specific B cell and T cell responses and their T cell receptors (TCR) repertoires across 2 y postinfection in people with long COVID. Using 13 SARS-CoV-2 peptide-HLA tetramers, spanning 11 HLA allotypes, as well as spike and nucleocapsid probes, we tracked SARS-CoV-2-specific CD8+ and CD4+ T cells and B-cells in individuals from their first SARS-CoV-2 infection through primary vaccination over 24 mo. The frequencies of ORF1a- and nucleocapsid-specific T cells and B cells remained stable over 24 mo. Spike-specific CD8+ and CD4+ T cells and B cells were boosted by SARS-CoV-2 vaccination, indicating immunization, in fully recovered and people with long COVID, altered the immunodominance hierarchy of SARS-CoV-2 T cell epitopes. Meanwhile, influenza-specific CD8+ T cells were stable across 24 mo, suggesting no bystander-activation. Compared to total T cell populations, SARS-CoV-2-specific T cells were enriched for central memory phenotype, although the proportion of central memory T cells decreased following acute illness. Importantly, TCR repertoire composition was maintained throughout long COVID, including postvaccination, to 2 y postinfection. Overall, we defined ex vivo SARS-CoV-2-specific B cells and T cells to understand primary and recall responses, providing key insights into antigen-specific responses in people with long COVID.
URI: https://ahro.austin.org.au/austinjspui/handle/1/35517
DOI: 10.1073/pnas.2411428121
ORCID: 0000-0002-0649-5089
0000-0002-3755-159X
0000-0001-5904-1905
0000-0003-1064-3934
0000-0002-5593-9387
0000-0002-8539-4891
0000-0002-2020-7522
0000-0001-8217-5995
0000-0002-9101-7953
0000-0001-6141-335X
0000-0002-9294-7693
Journal: Proceedings of the National Academy of Sciences of the United States of America
Start page: e2411428121
PubMed URL: 39284068
ISSN: 1091-6490
Type: Journal Article
Subjects: SARS-CoV-2 epitopes
T cell receptors
T cells
long COVID
CD8-Positive T-Lymphocytes/immunology
SARS-CoV-2/immunology
COVID-19/immunology
Receptors, Antigen, T-Cell/immunology
Receptors, Antigen, T-Cell/metabolism
Epitopes, T-Lymphocyte/immunology
Spike Glycoprotein, Coronavirus/immunology
B-Lymphocytes/immunology
Immunologic Memory/immunology
Coronavirus Nucleocapsid Proteins/immunology
Appears in Collections:Journal articles

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