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

journal contribution
posted on 2023-05-21, 02:53 authored by 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, Katie FlanaganKatie Flanagan, Sabrina SondaSabrina Sonda, Jasveen Kaur, 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, Kedzierska, K
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.

History

Publication title

Immunity

Volume

54

Issue

5

Pagination

1066-1082

ISSN

1074-7613

Department/School

Tasmanian School of Medicine

Publisher

Cell Press

Place of publication

1100 Massachusetts Ave, Cambridge, USA, Ma, 02138

Rights statement

Copyright 2021 Elsevier Inc.

Repository Status

  • Restricted

Socio-economic Objectives

Diagnosis of human diseases and conditions

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