tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2024 Sep 24;121(39):e2411428121.
doi: 10.1073/pnas.2411428121. Epub 2024 Sep 16. SARS-CoV-2-specific CD8[SUP]+[/SUP] T cells from people with long COVID establish and maintain effector phenotype and key TCR signatures over 2 years
Louise C Rowntree[SUP] #[/SUP][SUP] 1 [/SUP], Jennifer Audsley[SUP] #[/SUP][SUP] 2 [/SUP], Lilith F Allen[SUP] 1 [/SUP], Hayley A McQuilten[SUP] 1 [/SUP], Ruth R Hagen[SUP] 1 [/SUP], Priyanka Chaurasia[SUP] 3 [/SUP], Jan Petersen[SUP] 3 [/SUP], Dene R Littler[SUP] 3 [/SUP], Hyon-Xhi Tan[SUP] 1 [/SUP], Lydia Murdiyarso[SUP] 1 [/SUP], Jennifer R Habel[SUP] 1 [/SUP], Isabelle J H Foo[SUP] 1 [/SUP], Wuji Zhang[SUP] 1 [/SUP], Elizabeth R V Ten Berge[SUP] 1 [/SUP], Hanujah Ganesh[SUP] 2 [/SUP], Prathanporn Kaewpreedee[SUP] 4 [/SUP], Kelly W K Lee[SUP] 4 [/SUP], Samuel M S Cheng[SUP] 5 [/SUP], Janette S Y Kwok[SUP] 6 [/SUP], Dhilshan Jayasinghe[SUP] 7 8 [/SUP], Stephanie Gras[SUP] 3 7 8 [/SUP], Jennifer A Juno[SUP] 1 [/SUP], Adam K Wheatley[SUP] 1 [/SUP], Stephen J Kent[SUP] 1 [/SUP], Jamie Rossjohn[SUP] 3 9 [/SUP], Allen C Cheng[SUP] 10 11 [/SUP], Tom C Kotsimbos[SUP] 12 13 [/SUP], Jason A Trubiano[SUP] 2 14 15 16 17 [/SUP], Natasha E Holmes[SUP] 17 18 19 [/SUP], Ken Ka Pang Chan[SUP] 20 21 [/SUP], David S C Hui[SUP] 20 21 [/SUP], Malik Peiris[SUP] 4 5 22 [/SUP], Leo L M Poon[SUP] 4 5 22 [/SUP], Sharon R Lewin[SUP] 2 23 24 [/SUP], Peter C Doherty[SUP] #[/SUP][SUP] 1 [/SUP], Irani Thevarajan[SUP] #[/SUP][SUP] 2 23 [/SUP], Sophie A Valkenburg[SUP] #[/SUP][SUP] 1 4 [/SUP], Katherine Kedzierska[SUP] #[/SUP][SUP] 1 [/SUP], Thi H O Nguyen[SUP] #[/SUP][SUP] 1 [/SUP]
Affiliations
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[SUP]+[/SUP] and CD4[SUP]+[/SUP] 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[SUP]+[/SUP] and CD4[SUP]+[/SUP] 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[SUP]+[/SUP] 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.
Keywords: SARS-CoV-2 epitopes; T cell receptors; T cells; long COVID.
. 2024 Sep 24;121(39):e2411428121.
doi: 10.1073/pnas.2411428121. Epub 2024 Sep 16. SARS-CoV-2-specific CD8[SUP]+[/SUP] T cells from people with long COVID establish and maintain effector phenotype and key TCR signatures over 2 years
Louise C Rowntree[SUP] #[/SUP][SUP] 1 [/SUP], Jennifer Audsley[SUP] #[/SUP][SUP] 2 [/SUP], Lilith F Allen[SUP] 1 [/SUP], Hayley A McQuilten[SUP] 1 [/SUP], Ruth R Hagen[SUP] 1 [/SUP], Priyanka Chaurasia[SUP] 3 [/SUP], Jan Petersen[SUP] 3 [/SUP], Dene R Littler[SUP] 3 [/SUP], Hyon-Xhi Tan[SUP] 1 [/SUP], Lydia Murdiyarso[SUP] 1 [/SUP], Jennifer R Habel[SUP] 1 [/SUP], Isabelle J H Foo[SUP] 1 [/SUP], Wuji Zhang[SUP] 1 [/SUP], Elizabeth R V Ten Berge[SUP] 1 [/SUP], Hanujah Ganesh[SUP] 2 [/SUP], Prathanporn Kaewpreedee[SUP] 4 [/SUP], Kelly W K Lee[SUP] 4 [/SUP], Samuel M S Cheng[SUP] 5 [/SUP], Janette S Y Kwok[SUP] 6 [/SUP], Dhilshan Jayasinghe[SUP] 7 8 [/SUP], Stephanie Gras[SUP] 3 7 8 [/SUP], Jennifer A Juno[SUP] 1 [/SUP], Adam K Wheatley[SUP] 1 [/SUP], Stephen J Kent[SUP] 1 [/SUP], Jamie Rossjohn[SUP] 3 9 [/SUP], Allen C Cheng[SUP] 10 11 [/SUP], Tom C Kotsimbos[SUP] 12 13 [/SUP], Jason A Trubiano[SUP] 2 14 15 16 17 [/SUP], Natasha E Holmes[SUP] 17 18 19 [/SUP], Ken Ka Pang Chan[SUP] 20 21 [/SUP], David S C Hui[SUP] 20 21 [/SUP], Malik Peiris[SUP] 4 5 22 [/SUP], Leo L M Poon[SUP] 4 5 22 [/SUP], Sharon R Lewin[SUP] 2 23 24 [/SUP], Peter C Doherty[SUP] #[/SUP][SUP] 1 [/SUP], Irani Thevarajan[SUP] #[/SUP][SUP] 2 23 [/SUP], Sophie A Valkenburg[SUP] #[/SUP][SUP] 1 4 [/SUP], Katherine Kedzierska[SUP] #[/SUP][SUP] 1 [/SUP], Thi H O Nguyen[SUP] #[/SUP][SUP] 1 [/SUP]
Affiliations
- PMID: 39284068
- DOI: 10.1073/pnas.2411428121
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[SUP]+[/SUP] and CD4[SUP]+[/SUP] 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[SUP]+[/SUP] and CD4[SUP]+[/SUP] 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[SUP]+[/SUP] 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.
Keywords: SARS-CoV-2 epitopes; T cell receptors; T cells; long COVID.