CD8 T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope display high naive precursor frequency and TCR promiscuity

THO Nguyen; LC Rowntree; J Petersen; BY Chua; L Hensen; L Kedzierski; CE van de Sandt; P Chaurasia; HX Tan; JR Habel; W Zhang; LF Allen; L Earnest; KY Mak; JA Juno; K Wragg; FL Mordant; F Amanat; F Krammer; NA Mifsud; DL Doolan; KL Flanagan; S Sonda; J Kaur; LM Wakim; GP Westall; F James; E Mouhtouris; CL Gordon; NE Holmes; OC Smibert; JA Trubiano; AC Cheng; P Harcourt; P Clifton; JC Crawford; PG Thomas; AK Wheatley; SJ Kent; J Rossjohn; J Torresi; K Kedzierska

Journal article

CD8 T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope display high naive precursor frequency and TCR promiscuity

THO Nguyen, LC Rowntree, J Petersen, BY Chua, L Hensen, L Kedzierski, CE van de Sandt, P Chaurasia, HX Tan, JR Habel, W Zhang, LF Allen, L Earnest, KY Mak, JA Juno, K Wragg, FL Mordant, F Amanat, F Krammer, NA Mifsud Show all

Immunity | CELL PRESS | Published : 2021

DOI: 10.1016/j.immuni.2021.04.009

Abstract

To better understand primary and recall T cell responses during coronavirus disease 2019 (COVID-19), it is important to examine unmanipulated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells. By using peptide-human leukocyte antigen (HLA) tetramers for direct ex vivo analysis, we characterized CD8+ T cells specific for SARS-CoV-2 epitopes in COVID-19 patients and unexposed individuals. Unlike CD8+ T cells directed toward subdominant epitopes (B7/N257, A2/S269, and A24/S1,208) CD8+ T cells specific for the immunodominant B7/N105 epitope were detected at high frequencies in pre-pandemic samples and at increased frequencies during acute COVID-19 and convalescence. S..

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University of Melbourne Researchers

Oanh Nguyen Author

Louise Rowntree Author

Brendon Chua Author

Lukasz Kedzierski Author

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Grants

Awarded by Australian Research Council

Funding Acknowledgements

We thank all the participants involved in the study, as well as Robyn Esterbauer, Hannah Kelly, Jane Batten, Helen Kent, and Kanta Subbarao for support with the cohorts and assays. We thank Jill Garlick, Janine Roney, Anne Paterson, and the research nurses at the Alfred Hospital. We acknowledge all DRASTIC (The use of cytokines as a preDictoR of disease Severity in criTically Ill Covid-patients) investigators from Austin Health and thank the participants involved. We thank Ana Copaescu for laboratory work and study coordination for the DRASTIC study. We thank Thomas Loudovaris and Stuart I. Mannering from St Vincent's Institute of Medical Research for access to spleen samples. This work was supported by the Clifford Craig Foundation to K.L.F. and K.K.; an NHMRC Leadership Investigator Grant to K.K. (1173871); an NHMRC Emerging Leadership Level 1 Investigator Grant to THON (1194036); an NHMRC program grant to D.L.D. (1132975); the Research Grants Council of the Hong Kong Special Administrative Region, China (T11-712/19-N) to K.K.; the Victorian government to S.J.K. and A.K.W.; an MRFF award (2002073) to S.J.K. and A.K.W.; an MRFF award (1202445) to K.K.; an MRFF award (2005544) to K.K., S.J.K., J.A.J., and A.K.W.; an NHMRC program grant (1149990) to S.J.K.; an NHMRC project grant (1162760) to A.K.W.; and NIH contract CIVR-HRP (HHS-NIH-NIAID-BAA2018) to P.G.T. and K.K. A.K.W. is supported by an Emerging Leadership 1 Investigator Grant (1173433), J.A.J. by an NHMRC Early Career Fellowship (ECF) (1123673), D.L.D. by an NHMRC Principal Research Fellowship (1137285), and S.J.K. by an NHMRC Senior Principal Research Fellowship (1136322). C.E.S. has received funding from the European Union's Horizon 2020 research, innovation program under the Marie Sk1odowska-Curie grant agreement (792532) and the Doherty Collaborative Seed Grant. J.R. is supported by an ARC Laureate fellowship. J.R.H. and W.Z. are supported by the Melbourne Research Scholarship from the University of Melbourne. L.H. is supported by the Melbourne International Research Scholarship (MIRS) and the Melbourne International Fee Remission Scholarship (MIFRS) from The University of Melbourne. J.C.C. and P.G.T. are supported by NIH NIAID (R01 AI136514-03) and ALSAC at St. Jude.