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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, 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 ORCID: 0000-0001-8152-3425, 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 and Kedzierska, K 2021 , 'CD8 + T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope display high naive precursor frequency and TCR promiscuity' , Immunity, vol. 54, no. 5 , 1066–1082 , doi: 10.1016/j.immuni.2021.04.009.

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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. 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 Type: Article
Authors/Creators: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
Keywords: COVID-19, SARS-CoV-2-specific CD8+, T cells, TCR, immunodominant
Journal or Publication Title: Immunity
Publisher: Cell Press
ISSN: 1074-7613
DOI / ID Number: 10.1016/j.immuni.2021.04.009
Copyright Information:

Copyright 2021 Elsevier Inc.

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