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

Nguyen, Thi H.O., Rowntree, Louise C., Petersen, Jan, Chua, Brendon Y., Hensen, Luca, Kedzierski, Lukasz, van de Sandt, Carolien E., Chaurasia, Priyanka, Tan, Hyon Xhi, Habel, Jennifer R., Zhang, Wuji, Allen, Lilith F., Earnest, Linda, Mak, Kai Yan, Juno, Jennifer A., Wragg, Kathleen, Mordant, Francesca L., Amanat, Fatima, Krammer, Florian, Mifsud, Nicole A., Doolan, Denise L., Flanagan, Katie L., Sonda, Sabrina, Kaur, Jasveen, Wakim, Linda M., Westall, Glen P., James, Fiona, Mouhtouris, Effie, Gordon, Claire L., Holmes, Natasha E., Smibert, Olivia C., Trubiano, Jason A., Cheng, Allen C., Harcourt, Peter, Clifton, Patrick, Crawford, Jeremy Chase, Thomas, Paul G., Wheatley, Adam K., Kent, Stephen J., Rossjohn, Jamie, Torresi, Joseph, and Kedzierska, Katherine (2021) CD8+ T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope display high naive precursor frequency and TCR promiscuity. Immunity, 54 (5). 1066-1082.e5.

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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 ID: 70403
Item Type: Article (Research - C1)
ISSN: 1097-4180
Keywords: COVID-19, immunodominant, SARS-CoV-2-specific CD8+, T cells, TCR
Copyright Information: © 2021 Elsevier Inc.
Funders: National Health and Medical Research Council (NHMRC), Australian Research Council (ARC)
Projects and Grants: NHMRC 1173871, NHMRC 1194036, NHMRC 1132975, NHMRC 1149990, NHMRC 1162760, NHMRC 1137285, NHMRC 1136322
Date Deposited: 28 Apr 2022 06:26
Downloads: Total: 1
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