TY - JOUR
AU - Rowntree, Louise C.
AU - Allen, Lilith F.
AU - Hagen, Ruth R.
AU - McQuilten, Hayley A.
AU - Quadeer, Ahmed A.
AU - Chaurasia, Priyanka
AU - Kaewpreedee, Prathanporn
AU - Lee, Kelly W.K.
AU - Cohen, Carolyn A.
AU - Petersen, Jan
AU - Littler, Dene R.
AU - Habel, Jennifer R.
AU - Zhang, Wuji
AU - Cheng, Samuel M.S.
AU - Chan, Ken Ka Pang
AU - Kwok, Janette S.Y.
AU - Leung, Kathy S.M.
AU - Wu, Joseph T.
AU - Lee, Cheuk-Kwong
AU - Davies, Jane
AU - Pannaraj, Pia S.
AU - Kaity Allen, E.
AU - Thomas, Paul G.
AU - Tosif, Shidan
AU - Crawford, Nigel
AU - Lappas, Martha
AU - Thevarajan, Irani
AU - Lewin, Sharon R.
AU - Kent, Stephen J.
AU - Juno, Jennifer A.
AU - Bond, Katherine A.
AU - Williamson, Deborah A.
AU - Holmes, Natasha E.
AU - Smibert, Olivia C.
AU - Gordon, Claire
AU - Trubiano, Jason A.
AU - Kotsimbos, Tom C.
AU - Cheng, Allen C.
AU - Efstathiou, Claudia
AU - Turtle, Lance C.W.
AU - Thwaites, Ryan S.
AU - Brightling, Christopher E.
AU - The PHOSP-COVID Collaborative Group
AU - Rossjohn, Jamie
AU - McKay, Matthew R.
AU - Tian, Jinmin
AU - Lui, William Jun
AU - Gao, George Fu
AU - Xu, Jianqing
AU - Sonehara, Kyuto
AU - Ishii, Ken J.
AU - Namkoong, Ho
AU - Okada, Yukinori
AU - Peiris, Malik
AU - Hui, David S.C.
AU - Poon, Leo L.M.
AU - Doherty, Peter C.
AU - Nguyen, Thi Ho
AU - Valkenburg, Sophie A.
AU - Kedzierska, Katherine
PY - 2025
DA - September
TI - HLA-B*15:01-positive severe COVID-19 patients lack CD8+ T cell pools with highly expanded public clonotypes
JO - Proceedings of the National Academy of Sciences
VL - 122
IS - 36
DO - https://doi.org/10.1073/pnas.2503145122
AB - Understanding host factors driving asymptomatic versus severe disease outcomes is of key importance if we are to control emerging and re-emerging viral infections. HLA-B*15:01 has been associated with asymptomatic SARS-CoV-2 infection in nonhospitalized individuals of European ancestry, with protective immunity attributed to preexisting cross-reactive CD8+ T-cells directed against HLA-B*15:01-restricted Spike-derived S919-927 peptide (B15/S919+CD8+ T-cells). However, fundamental questions remained on the abundance and clonotypic nature of CD8+ T-cell responses in HLA-B*15:01-positive patients who succumbed to life-threatening COVID-19. Here, we analyzed B15/S919+CD8+ T-cell responses in COVID-19 patients from independent HLA-typed COVID-19 patient cohorts across three continents, Australia, Asia and Europe. We assessed B15/S919+CD8+ T-cells in COVID-19 patients across disease outcomes ranging from asymptomatic to hospitalized critical illness. We found that severe/critical COVID-19 patients mounted B15/S919+CD8+ T-cell responses lacking a highly expanded key public B15/S919+CD8+ T-cell receptor (TCR; TRAV9-2/TRBV7-2) which recurred across multiple individuals in COVID-19 patients with a mild disease. Instead, B15/S919+CD8+ T-cell responses in life-threatening disease had a prevalence of an alternate TCR clonotypic motif (TRAV38-2/DV8/TRBV20-1), potentially contributing, at least in part, to why B15/S919+CD8+ T-cells in severe COVID-19 patients were less protective. Interestingly, the frequency, memory phenotype, and activation profiles of circulating B15/S919+CD8+ T-cells did not differ across disease severity. Moreover, B15/S919+CD8+ T-cells were better maintained into convalescence compared to other SARS-CoV-2-specificities. Our study thus provides evidence on the differential nature of the TCR clonal repertoire in 22.37% of HLA-B*15:01-positive COVID-19 patients who developed severe or critical disease in our cohorts, comparing to HLA-B*15:01-expressing individuals with mild COVID-19.
PB - National Academy of Sciences
UR - https://research-portal.st-andrews.ac.uk/en/publications/hla-b1501-positive-severe-covid-19-patients-lack-cd8supsup-t-cell/
KW - Coronavirus (COVID-19)
ER