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


Nguyen, THO and Rowntree, LC and Petersen, J and Chua, BY and Hensen, L and Kedzierski, L and van de Sandt, CE and Chaurasia, P and Tan, H-X and Habel, JR and Zhang, W and Allen, LF and Earnest, L and Mak, KY and Juno, JA and Wragg, K and Mordant, FL and Amanat, F and Krammer, F and Mifsud, NA and Doolan, DL and Flanagan, K and Sonda, S and Kaur, J and Wakim, LM and Westall, GP and James, F and Mouhtouris, E and Gordon, CL and Holmes, NE and Smibert, OC and Trubiano, JA and Cheng, AC and Harcourt, P and Clifton, P and Crawford, JC and Thomas, PG and Wheatley, AK and Kent, SJ and Rossjohn, J and Torresi, J and Kedzierska, K, CD8 + T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope display high naive precursor frequency and TCR promiscuity, Immunity, 54, (5) pp. 1066-1082. ISSN 1074-7613 (2021) [Refereed Article]

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Copyright 2021 Elsevier Inc.

DOI: doi:10.1016/j.immuni.2021.04.009


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. SARS-CoV-2-specific CD8+ T cells in pre-pandemic samples from children, adults, and elderly individuals predominantly displayed a naive phenotype, indicating a lack of previous cross-reactive exposures. T cell receptor (TCR) analyses revealed diverse TCRαβ repertoires and promiscuous αβ-TCR pairing within B7/N105+CD8+ T cells. Our study demonstrates high naive precursor frequency and TCRαβ diversity within immunodominant B7/N105-specific CD8+ T cells and provides insight into SARS-CoV-2-specific T cell origins and subsequent responses.

Item Details

Item Type:Refereed Article
Keywords:COVID-19, SARS-CoV-2-specific CD8+, T cells, TCR, immunodominant
Research Division:Biomedical and Clinical Sciences
Research Group:Cardiovascular medicine and haematology
Research Field:Respiratory diseases
Objective Division:Health
Objective Group:Clinical health
Objective Field:Diagnosis of human diseases and conditions
UTAS Author:Flanagan, K (Dr Katie Flanagan)
UTAS Author:Sonda, S (Dr Sabrina Sonda)
UTAS Author:Kaur, J (Ms Jasveen Kaur)
ID Code:146881
Year Published:2021
Web of Science® Times Cited:44
Deposited By:Medicine
Deposited On:2021-10-01
Last Modified:2022-08-25

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