HLA-B*15:01-positive severe COVID-19 patients lack CD8 T cell pools with highly expanded public clonotypes

LC Rowntree; LF Allen; RR Hagen; HA McQuilten; AA Quadeer; P Chaurasia; P Kaewpreedee; KWK Lee; CA Cohen; J Petersen; DR Littler; JR Habel; W Zhang; SMS Cheng; KKP Chan; JSY Kwok; KSM Leung; JT Wu; CK Lee; J Davies; PS Pannaraj; E Kaity Allen; PG Thomas; S Tosif; NW Crawford; M Lappas; I Thevarajan; SR Lewin; SJ Kent; JA Juno; KA Bond; DA Williamson; NE Holmes; OC Smibert; CL Gordon; JA Trubiano; TC Kotsimbos; AC Cheng; C Efstathiou; L Turtle; RS Thwaites; CE Brightling; J Rossjohn; MR McKay; J Tian; WJ Liu; GF Gao; J Xu; K Sonehara; KJ Ishii; H Namkoong; Y Okada; M Peiris; DSC Hui; LLM Poon; PC Doherty; THO Nguyen; SA Valkenburg; K Kedzierska

Journal article

HLA-B*15:01-positive severe COVID-19 patients lack CD8 T cell pools with highly expanded public clonotypes

LC Rowntree, LF Allen, RR Hagen, HA McQuilten, AA Quadeer, P Chaurasia, P Kaewpreedee, KWK Lee, CA Cohen, J Petersen, DR Littler, JR Habel, W Zhang, SMS Cheng, KKP Chan, JSY Kwok, KSM Leung, JT Wu, CK Lee, J Davies Show all

Proceedings of the National Academy of Sciences of the United States of America | Published : 2025

DOI: 10.1073/pnas.2503145122

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Abstract

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 COVI..

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