{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:20:39Z","timestamp":1792196439139,"version":"4.4.0"},"reference-count":40,"publisher":"National Academy of Sciences","issue":"36","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"Federal Government | DHAC | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1173871"],"award-info":[{"award-number":["1173871"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,9,9]]},"abstract":"<jats:p>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    T-cells directed against HLA-B*15:01-restricted Spike-derived S\n                    <jats:sub>919-927<\/jats:sub>\n                    peptide (B15\/S\n                    <jats:sub>919<\/jats:sub>\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cells). However, fundamental questions remained on the abundance and clonotypic nature of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell responses in HLA-B*15:01-positive patients who succumbed to life-threatening COVID-19. Here, we analyzed B15\/S\n                    <jats:sub>919<\/jats:sub>\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    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\/S\n                    <jats:sub>919<\/jats:sub>\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    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\/S\n                    <jats:sub>919<\/jats:sub>\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell responses lacking a highly expanded key public B15\/S\n                    <jats:sub>919<\/jats:sub>\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell receptor (TCR; TRAV9-2\/TRBV7-2) which recurred across multiple individuals in COVID-19 patients with a mild disease. Instead, B15\/S\n                    <jats:sub>919<\/jats:sub>\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    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\/S\n                    <jats:sub>919<\/jats:sub>\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cells in severe COVID-19 patients were less protective. Interestingly, the frequency, memory phenotype, and activation profiles of circulating B15\/S\n                    <jats:sub>919<\/jats:sub>\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cells did not differ across disease severity. Moreover, B15\/S\n                    <jats:sub>919<\/jats:sub>\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2503145122","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T18:00:10Z","timestamp":1756836010000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":5,"title":["HLA-B*15:01-positive severe COVID-19 patients lack CD8\n                    <sup>+<\/sup>\n                    T cell pools with highly expanded public clonotypes"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0649-5089","authenticated-orcid":false,"given":"Louise C.","family":"Rowntree","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilith F.","family":"Allen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth R.","family":"Hagen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayley A.","family":"McQuilten","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed A.","family":"Quadeer","sequence":"additional","affiliation":[{"name":"Department of Electronic and Computer Engineering, School of Engineering, Hong Kong University of Science and Technology, Hong Kong Special Administrative Region","place":["Hong Kong, China"]},{"name":"Department of Electrical and Electronic Engineering, University of Melbourne","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3755-159X","authenticated-orcid":false,"given":"Priyanka","family":"Chaurasia","sequence":"additional","affiliation":[{"name":"Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University","place":["Clayton, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prathanporn","family":"Kaewpreedee","sequence":"additional","affiliation":[{"name":"HKU-Pasteur Research Pole, School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region","place":["Hong Kong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly W. K.","family":"Lee","sequence":"additional","affiliation":[{"name":"HKU-Pasteur Research Pole, School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region","place":["Hong Kong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn A.","family":"Cohen","sequence":"additional","affiliation":[{"name":"HKU-Pasteur Research Pole, School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region","place":["Hong Kong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Petersen","sequence":"additional","affiliation":[{"name":"Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University","place":["Clayton, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5904-1905","authenticated-orcid":false,"given":"Dene R.","family":"Littler","sequence":"additional","affiliation":[{"name":"Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University","place":["Clayton, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer R.","family":"Habel","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wuji","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7293-2331","authenticated-orcid":false,"given":"Samuel M. S.","family":"Cheng","sequence":"additional","affiliation":[{"name":"Division of Public Health Laboratory Sciences, School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region","place":["Hong Kong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken Ka Pang","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong","place":["Hong Kong Special Administrative Region, China"]},{"name":"Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region","place":["Hong Kong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janette S. Y.","family":"Kwok","sequence":"additional","affiliation":[{"name":"Division of Transplantation and Immunogenetics, Department of Pathology, Queen Mary Hospital, Hong Kong Special Administrative Region","place":["Hong Kong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4777-388X","authenticated-orcid":false,"given":"Kathy S. M.","family":"Leung","sequence":"additional","affiliation":[{"name":"The Hong Kong Jockey Club Global Health Institute, Hong Kong Special Administrative Region","place":["Hong Kong, China"]},{"name":"WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region","place":["Hong Kong, China"]},{"name":"Laboratory of Data Discovery for Health, Hong Kong Science Park, Hong Kong Special Administrative Region","place":["Hong Kong, China"]},{"name":"The University of Hong Kong - Shenzhen Hospital","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3155-5987","authenticated-orcid":false,"given":"Joseph T.","family":"Wu","sequence":"additional","affiliation":[{"name":"The Hong Kong Jockey Club Global Health Institute, Hong Kong Special Administrative Region","place":["Hong Kong, China"]},{"name":"WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region","place":["Hong Kong, China"]},{"name":"Laboratory of Data Discovery for Health, Hong Kong Science Park, Hong Kong Special Administrative Region","place":["Hong Kong, China"]},{"name":"The University of Hong Kong - Shenzhen Hospital","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheuk-Kwong","family":"Lee","sequence":"additional","affiliation":[{"name":"The Hong Kong Jockey Club Global Health Institute, Hong Kong Special Administrative Region","place":["Hong Kong, China"]},{"name":"WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region","place":["Hong Kong, China"]},{"name":"Laboratory of Data Discovery for Health, Hong Kong Science Park, Hong Kong Special Administrative Region","place":["Hong Kong, China"]},{"name":"The University of Hong Kong - Shenzhen Hospital","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Davies","sequence":"additional","affiliation":[{"name":"Menzies School of Health Research","place":["Darwin, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia S.","family":"Pannaraj","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Children\u2019s Hospital Los Angeles","place":["Los Angeles"]},{"name":"Department of Pediatrics, Molecular Microbiology and Immunology, Keck School of Medicine, The University of California","place":["Los Angeles"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Kaity Allen","sequence":"additional","affiliation":[{"name":"Department of Immunology, St. Jude Children\u2019s Research Hospital","place":["Memphis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7955-0256","authenticated-orcid":false,"given":"Paul G.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Immunology, St. Jude Children\u2019s Research Hospital","place":["Memphis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shidan","family":"Tosif","sequence":"additional","affiliation":[{"name":"Infection and Immunity, Murdoch Children\u2019s Research Institute","place":["Melbourne, Australia"]},{"name":"Department of Paediatrics, University of Melbourne","place":["Melbourne, Australia"]},{"name":"Department of General Medicine, Royal Children\u2019s Hospital Melbourne","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel W.","family":"Crawford","sequence":"additional","affiliation":[{"name":"Infection and Immunity, Murdoch 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Infection and Immunity","place":["Melbourne, Australia"]},{"name":"ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne","place":["Melbourne, Australia"]},{"name":"Melbourne Sexual Health Centre, Infectious Diseases Department, Alfred Health, Central Clinical School, Monash University","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9072-1017","authenticated-orcid":false,"given":"Jennifer A.","family":"Juno","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A.","family":"Bond","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity","place":["Melbourne, Australia"]},{"name":"Victorian Infectious Diseases Reference Laboratory, at the Peter Doherty Institute for Infection and Immunity","place":["Melbourne, Australia"]},{"name":"Department of Microbiology, Royal Melbourne Hospital","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah A.","family":"Williamson","sequence":"additional","affiliation":[{"name":"Victorian Infectious Diseases Service, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity","place":["Melbourne, Australia"]},{"name":"Victorian Infectious Diseases Reference Laboratory, at the Peter Doherty Institute for Infection and Immunity","place":["Melbourne, Australia"]},{"name":"School of Medicine, University of St Andrews","place":["Scotland, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha E.","family":"Holmes","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity","place":["Melbourne, Australia"]},{"name":"Department of Infectious Diseases and Immunology, Austin Health","place":["Heidelberg, Australia"]},{"name":"Data Analytics Research and Evaluation Centre, Austin Health and University of Melbourne","place":["Heidelberg, Australia"]},{"name":"Department of Infectious Diseases, Centre for Antibiotic Allergy and Research, Austin Health","place":["Heidelberg, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia C.","family":"Smibert","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Immunology, Austin Health","place":["Heidelberg, Australia"]},{"name":"Department of Infectious Diseases, Peter MacCallum Cancer Centre","place":["Melbourne, Australia"]},{"name":"National Centre for Infections in Cancer, Peter McCallum Cancer Centre","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire L.","family":"Gordon","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity","place":["Melbourne, Australia"]},{"name":"Department of Infectious Diseases and Immunology, Austin Health","place":["Heidelberg, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason A.","family":"Trubiano","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity","place":["Melbourne, Australia"]},{"name":"Department of Infectious Diseases, Centre for Antibiotic Allergy and Research, Austin Health","place":["Heidelberg, Australia"]},{"name":"Department of Infectious Diseases, Peter MacCallum Cancer Centre","place":["Melbourne, Australia"]},{"name":"National Centre for Infections in Cancer, Peter McCallum Cancer Centre","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom C.","family":"Kotsimbos","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, The Alfred Hospital","place":["Melbourne, Australia"]},{"name":"Department of Medicine, Central Clinical School, The Alfred Hospital, Monash University","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen C.","family":"Cheng","sequence":"additional","affiliation":[{"name":"School of Public Health and Preventive Medicine, Monash University","place":["Clayton, Australia"]},{"name":"Monash Infectious Diseases, Monash Health and School of Clinical Sciences, Monash University","place":["Clayton, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Efstathiou","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, 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Special Administrative Region","place":["Hong Kong, China"]},{"name":"Department of Electrical and Electronic Engineering, University of Melbourne","place":["Melbourne, Australia"]},{"name":"Victorian Infectious Diseases Reference Laboratory, at the Peter Doherty Institute for Infection and Immunity","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinmin","family":"Tian","sequence":"additional","affiliation":[{"name":"National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William Jun","family":"Liu","sequence":"additional","affiliation":[{"name":"National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention","place":["Beijing, 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Genome Informatics, Graduate School of Medicine, University of Tokyo","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6728-3872","authenticated-orcid":false,"given":"Ken J.","family":"Ishii","sequence":"additional","affiliation":[{"name":"Laboratory of Adjuvant Innovation, Center for Vaccine and Adjuvant Research, National Institutes of Biomedical Innovation, Health and Nutrition, Saito Asagi","place":["Ibaraki, Japan"]},{"name":"Division of Vaccine Science, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Minato-ku","place":["Tokyo, Japan"]},{"name":"Department of Immunopathology, Immunology Frontier Research Center, Osaka University","place":["Suita, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho","family":"Namkoong","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Keio University School of 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China"]},{"name":"Division of Public Health Laboratory Sciences, School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region","place":["Hong Kong, China"]},{"name":"Centre for Immunology and Infection, Hong Kong Science and Technology Park, New Territories, Hong Kong Special Administrative Region","place":["Hong Kong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S. C.","family":"Hui","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong","place":["Hong Kong Special Administrative Region, China"]},{"name":"Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region","place":["Hong Kong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9101-7953","authenticated-orcid":false,"given":"Leo L. M.","family":"Poon","sequence":"additional","affiliation":[{"name":"HKU-Pasteur Research Pole, School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region","place":["Hong Kong, China"]},{"name":"Division of Public Health Laboratory Sciences, School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region","place":["Hong Kong, China"]},{"name":"Centre for Immunology and Infection, Hong Kong Science and Technology Park, New Territories, Hong Kong Special Administrative Region","place":["Hong Kong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter C.","family":"Doherty","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9294-7693","authenticated-orcid":false,"given":"Thi H. 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