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

Thi H.O. Nguyen, Louise C. Rowntree, Jan Petersen, Brendon Y. Chua, Luca Hensen, Lukasz Kedzierski, Carolien E. van de Sandt, Priyanka Chaurasia, Hyon Xhi Tan, Jennifer R. Habel, Wuji Zhang, Lilith F. Allen, Linda Earnest, Kai Yan Mak, Jennifer A. Juno, Kathleen Wragg, Francesca L. Mordant, Fatima Amanat, Florian Krammer, Nicole A. MifsudDenise L. Doolan, Katie L. Flanagan, Sabrina Sonda, Jasveen Kaur, Linda M. Wakim, Glen P. Westall, Fiona James, Effie Mouhtouris, Claire L. Gordon, Natasha E. Holmes, Olivia C. Smibert, Jason A. Trubiano, Allen C. Cheng, Peter Harcourt, Patrick Clifton, Jeremy Chase Crawford, Paul G. Thomas, Adam K. Wheatley, Stephen J. Kent, Jamie Rossjohn, Joseph Torresi, Katherine Kedzierska

Research output: Contribution to journalArticleResearchpeer-review

28 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1066-1082.e5
Number of pages23
JournalImmunity
Volume54
Issue number5
DOIs
Publication statusPublished - 11 May 2021

Keywords

  • COVID-19
  • immunodominant
  • SARS-CoV-2-specific CD8+
  • T cells
  • TCR

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