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

Journal Publication ResearchOnline@JCU
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;Kedzierska, Katherine
Denise Doolan
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.

Journal

Immunity

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54

ISBN/ISSN

1097-4180

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Issue

5

Pages Count

23

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Publisher

Cell Press

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DOI

10.1016/j.immuni.2021.04.009