CD8+ T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope display high naive precursor frequency and TCR promiscuity
Authors:
- 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
Details:
Immunity, Volume 54, Issue 5, 2021-05-11
Article Link: Click here
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.