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

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

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

Citation

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]

Copyright Statement

DOI: 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/S_1,208) 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:	27
Deposited By:	Medicine
Deposited On:	2021-10-01
Last Modified:	2021-11-19
Downloads:	0

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