Suboptimal SARS-CoV-2-specific CD8( ) T cell response associated with the prominent HLA-A*02:01 phenotype

Jennifer R Habel; Thi HO Nguyen; Carolien E van de Sandt; Jennifer A Juno; Priyanka Chaurasia; Kathleen Wragg; Marios Koutsakos; Luca Hensen; Xiaoxiao Jia; Brendon Chua; Wuji Zhang; Hyon-Xhi Tan; Katie L Flanagan; Denise L Doolan; Joseph Torresi; Weisan Chen; Linda M Wakim; Allen C Cheng; Peter C Doherty; Jan Petersen; Jamie Rossjohn; Adam K Wheatley; Stephen J Kent; Louise C Rowntree; Katherine Kedzierska

Journal article

Suboptimal SARS-CoV-2-specific CD8( ) T cell response associated with the prominent HLA-A*02:01 phenotype

Jennifer R Habel, Thi HO Nguyen, Carolien E van de Sandt, Jennifer A Juno, Priyanka Chaurasia, Kathleen Wragg, Marios Koutsakos, Luca Hensen, Xiaoxiao Jia, Brendon Chua, Wuji Zhang, Hyon-Xhi Tan, Katie L Flanagan, Denise L Doolan, Joseph Torresi, Weisan Chen, Linda M Wakim, Allen C Cheng, Peter C Doherty, Jan Petersen Show all

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | NATL ACAD SCIENCES | Published : 2020

DOI: 10.1073/pnas.2015486117

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Abstract

An improved understanding of human T cell-mediated immunity in COVID-19 is important for optimizing therapeutic and vaccine strategies. Experience with influenza shows that infection primes CD8+ T cell memory to peptides presented by common HLA types like HLA-A2, which enhances recovery and diminishes clinical severity upon reinfection. Stimulating peripheral blood mononuclear cells from COVID-19 convalescent patients with overlapping peptides from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the clonal expansion of SARS-CoV-2-specific CD8+ and CD4+ T cells in vitro, with CD4+ T cells being robust. We identified two HLA-A*02:01-restricted SARS-CoV-2-specfic CD8+ T cell..

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University of Melbourne Researchers

Jennifer Juno Author Microbiology and Immunology

Xiaoxiao Jia Author Microbiology and Immunology

Linda Wakim Author Microbiology and Immunology

Adam Wheatley Author Microbiology and Immunology

Stephen Kent Author Microbiology and Immunology

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Grants

Awarded by National Health and Medical Research Council (NHMRC)

Awarded by Research Grants Council of the Hong Kong Special Administrative Region, China

Awarded by Medical Research Future Fund (MRFF) Award

Awarded by European Union's Horizon 2020 research and innovation program under Marie Sklodowska-Curie Grant

Funding Acknowledgements

We thank all of the participants involved in the study, and Robyn Esterbauer, Hannah Kelly, Jane Batten, and Helen Kent for support with the cohort. We thank Jill Garlick, Janine Roney, Anne Paterson, and the research nurses at the Alfred Hospital. This work was supported by the Clifford Craig Foundation for K.L.F. and K.K.; National Health and Medical Research Council (NHMRC) Leadership Investigator Grant 1173871 to K.K.; NHMRC Program Grant 1132975 to D.L.D.; Research Grants Council of the Hong Kong Special Administrative Region, China (Grant T11-712/19-N) to K.K.; the Victorian Government (S.J.K., A.K.W.); Medical Research Future Fund (MRFF) Award 2002073 to S.J.K. and A.K.W.; MRFF Award 1202445 to K.K.; NHMRC program Grant 1149990 (S.J.K.); and NHMRC project Grant 1162760 (A.K.W.). A.C.C. is supported by NHMRC Career Development Fellowship 1140509, K.K. is supported by NHMRC Senior Research Fellowship 1102792, D.L.D. is supported by NHMRC Principal Research Fellowship 1137285, and S.J.K. is supported by NHMRC Senior Principal Research Fellowship 1136322. J.R. is supported by an Australian Research Council Laureate fellowship. J.R.H. is supported by the Melbourne Research Scholarship from The University of Melbourne. C.E.v.d.S. has received funding from the European Union's Horizon 2020 research and innovation program under Marie Sklodowska-Curie Grant Agreement 792532. L.H. is supported by the Melbourne International Research Scholarship and the Melbourne International Fee Remission Scholarship from The University of Melbourne. J.A.J. is supported by NHMRC Early Career Fellowship 1123673. W.Z. is supported by the Melbourne Research Scholarship from The University of Melbourne.