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

[tetano]

Immunity


. 2021 Apr 15;S1074-7613(21)00171-0.
doi: 10.1016/j.immuni.2021.04.009. Online ahead of print.
CD8 ⁺ T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope display high naive precursor frequency and TCR promiscuity


Thi H O Nguyen ¹ , Louise C Rowntree ¹ , Jan Petersen ² , Brendon Y Chua ³ , Luca Hensen ¹ , Lukasz Kedzierski ⁴ , Carolien E van de Sandt ⁵ , Priyanka Chaurasia ⁶ , Hyon-Xhi Tan ¹ , Jennifer R Habel ¹ , Wuji Zhang ¹ , Lilith F Allen ¹ , Linda Earnest ¹ , Kai Yan Mak ¹ , Jennifer A Juno ¹ , Kathleen Wragg ¹ , Francesca L Mordant ¹ , Fatima Amanat ⁷ , Florian Krammer ⁸ , Nicole A Mifsud ⁶ , Denise L Doolan ⁹ , Katie L Flanagan ¹⁰ , Sabrina Sonda ¹¹ , Jasveen Kaur ¹² , Linda M Wakim ¹ , Glen P Westall ¹³ , Fiona James ¹⁴ , Effie Mouhtouris ¹⁴ , Claire L Gordon ¹⁵ , Natasha E Holmes ¹⁶ , Olivia C Smibert ¹⁷ , Jason A Trubiano ¹⁸ , Allen C Cheng ¹⁹ , Peter Harcourt ²⁰ , Patrick Clifton ²⁰ , Jeremy Chase Crawford ²¹ , Paul G Thomas ²¹ , Adam K Wheatley ²² , Stephen J Kent ²³ , Jamie Rossjohn ²⁴ , Joseph Torresi ¹ , Katherine Kedzierska ²⁵



Affiliations

• PMID: 33951417
• DOI: 10.1016/j.immuni.2021.04.009

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/S_1,208) 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 TCR?? repertoires and promiscuous ??-TCR pairing within B7/N₁₀₅⁺CD8⁺ T cells. Our study demonstrates high naive precursor frequency and TCR?? diversity within immunodominant B7/N₁₀₅-specific CD8⁺ T cells and provides insight into SARS-CoV-2-specific T cell origins and subsequent responses.

Keywords: COVID-19; SARS-CoV-2-specific CD8+; T cells; TCR; immunodominant.