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

THO Nguyen, LC Rowntree, J Petersen, BY Chua… - Immunity, 2021 - cell.com
THO Nguyen, LC Rowntree, J Petersen, BY Chua, L Hensen, L Kedzierski, CE van de Sandt…
Immunity, 2021cell.com
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/N 257, A2/S 269, and A24/S 1,208) CD8+ T cells …
Summary
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.
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