SARS- CoV-2-specific CD8+T cells from people with long COVID establish and maintain effector phenotype and key TCR signatures over 2 years
成果类型：
Article
署名作者：
Rowntree, Louise C.; Audsley, Jennifer; Allen, Lilith F.; Mcquilten, HayleyA.; Hagen, Ruth R.; Chaurasia, Priyanka; Petersen, Jan; Littler, Dene R.; Tan, Hyon-Xhi; Murdiyarso, Lydia; Habel, Jennifer R.; Foo, IsabelleJ. 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, StephenJ.; Rossjohn, Jamie; Cheng, Allen C.; Kotsimbos, Tom C.; Trubiano, Jason A.; Holmes, Natasha E.; Chan, Ken Ka Pang; 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.
署名单位：
University of Melbourne; Peter Doherty Institute; University of Melbourne; Peter Doherty Institute; Monash University; Monash University; University of Hong Kong; University of Hong Kong; La Trobe University; La Trobe University; Cardiff University; Monash University; Monash University; Monash Health; Monash University; Florey Institute of Neuroscience & Mental Health; Howard Florey Institute Affiliates; Florey Institute of Neuroscience & Mental Health; Howard Florey Institute Affiliates; Monash University; Peter Maccallum Cancer Center; Peter Maccallum Cancer Center; University of Melbourne; Austin Research Institute; Florey Institute of Neuroscience & Mental Health; Howard Florey Institute Affiliates; Florey Institute of Neuroscience & Mental Health; Howard Florey Institute Affiliates; Austin Research Institute; University of Melbourne; University of Melbourne; Chinese University of Hong Kong; Prince of Wales Hospital; Chinese University of Hong Kong; Melbourne Health; Royal Melbourne Hospital; University of Melbourne; Peter Doherty Institute; Monash University; Florey Institute of Neuroscience & Mental Health; Howard Florey Institute Affiliates
刊物名称：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN/ISSBN：
0027-11122
DOI：
10.1073/pnas.2411428121
发表日期：
2024-09-24
关键词：
摘要：
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 post- vaccination, 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.