tetano
Editor, Senior Moderator
Immunity
. 2021 Apr 15;S1074-7613(21)00171-0.
doi: 10.1016/j.immuni.2021.04.009. Online ahead of print.
CD8 [SUP]+[/SUP] T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope display high naive precursor frequency and TCR promiscuity
Thi H O Nguyen[SUP] 1 [/SUP], Louise C Rowntree[SUP] 1 [/SUP], Jan Petersen[SUP] 2 [/SUP], Brendon Y Chua[SUP] 3 [/SUP], Luca Hensen[SUP] 1 [/SUP], Lukasz Kedzierski[SUP] 4 [/SUP], Carolien E van de Sandt[SUP] 5 [/SUP], Priyanka Chaurasia[SUP] 6 [/SUP], Hyon-Xhi Tan[SUP] 1 [/SUP], Jennifer R Habel[SUP] 1 [/SUP], Wuji Zhang[SUP] 1 [/SUP], Lilith F Allen[SUP] 1 [/SUP], Linda Earnest[SUP] 1 [/SUP], Kai Yan Mak[SUP] 1 [/SUP], Jennifer A Juno[SUP] 1 [/SUP], Kathleen Wragg[SUP] 1 [/SUP], Francesca L Mordant[SUP] 1 [/SUP], Fatima Amanat[SUP] 7 [/SUP], Florian Krammer[SUP] 8 [/SUP], Nicole A Mifsud[SUP] 6 [/SUP], Denise L Doolan[SUP] 9 [/SUP], Katie L Flanagan[SUP] 10 [/SUP], Sabrina Sonda[SUP] 11 [/SUP], Jasveen Kaur[SUP] 12 [/SUP], Linda M Wakim[SUP] 1 [/SUP], Glen P Westall[SUP] 13 [/SUP], Fiona James[SUP] 14 [/SUP], Effie Mouhtouris[SUP] 14 [/SUP], Claire L Gordon[SUP] 15 [/SUP], Natasha E Holmes[SUP] 16 [/SUP], Olivia C Smibert[SUP] 17 [/SUP], Jason A Trubiano[SUP] 18 [/SUP], Allen C Cheng[SUP] 19 [/SUP], Peter Harcourt[SUP] 20 [/SUP], Patrick Clifton[SUP] 20 [/SUP], Jeremy Chase Crawford[SUP] 21 [/SUP], Paul G Thomas[SUP] 21 [/SUP], Adam K Wheatley[SUP] 22 [/SUP], Stephen J Kent[SUP] 23 [/SUP], Jamie Rossjohn[SUP] 24 [/SUP], Joseph Torresi[SUP] 1 [/SUP], Katherine Kedzierska[SUP] 25 [/SUP]
Affiliations
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[SUP]+[/SUP] T cells specific for SARS-CoV-2 epitopes in COVID-19 patients and unexposed individuals. Unlike CD8[SUP]+[/SUP] T cells directed toward subdominant epitopes (B7/N[SUB]257[/SUB], A2/S[SUB]269[/SUB], and A24/S[SUB]1,208[/SUB]) CD8[SUP]+[/SUP] T cells specific for the immunodominant B7/N[SUB]105[/SUB] 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[SUP]+[/SUP] 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/N[SUB]105[/SUB][SUP]+[/SUP]CD8[SUP]+[/SUP] T cells. Our study demonstrates high naive precursor frequency and TCR?? diversity within immunodominant B7/N[SUB]105[/SUB]-specific CD8[SUP]+[/SUP] 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.
. 2021 Apr 15;S1074-7613(21)00171-0.
doi: 10.1016/j.immuni.2021.04.009. Online ahead of print.
CD8 [SUP]+[/SUP] T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope display high naive precursor frequency and TCR promiscuity
Thi H O Nguyen[SUP] 1 [/SUP], Louise C Rowntree[SUP] 1 [/SUP], Jan Petersen[SUP] 2 [/SUP], Brendon Y Chua[SUP] 3 [/SUP], Luca Hensen[SUP] 1 [/SUP], Lukasz Kedzierski[SUP] 4 [/SUP], Carolien E van de Sandt[SUP] 5 [/SUP], Priyanka Chaurasia[SUP] 6 [/SUP], Hyon-Xhi Tan[SUP] 1 [/SUP], Jennifer R Habel[SUP] 1 [/SUP], Wuji Zhang[SUP] 1 [/SUP], Lilith F Allen[SUP] 1 [/SUP], Linda Earnest[SUP] 1 [/SUP], Kai Yan Mak[SUP] 1 [/SUP], Jennifer A Juno[SUP] 1 [/SUP], Kathleen Wragg[SUP] 1 [/SUP], Francesca L Mordant[SUP] 1 [/SUP], Fatima Amanat[SUP] 7 [/SUP], Florian Krammer[SUP] 8 [/SUP], Nicole A Mifsud[SUP] 6 [/SUP], Denise L Doolan[SUP] 9 [/SUP], Katie L Flanagan[SUP] 10 [/SUP], Sabrina Sonda[SUP] 11 [/SUP], Jasveen Kaur[SUP] 12 [/SUP], Linda M Wakim[SUP] 1 [/SUP], Glen P Westall[SUP] 13 [/SUP], Fiona James[SUP] 14 [/SUP], Effie Mouhtouris[SUP] 14 [/SUP], Claire L Gordon[SUP] 15 [/SUP], Natasha E Holmes[SUP] 16 [/SUP], Olivia C Smibert[SUP] 17 [/SUP], Jason A Trubiano[SUP] 18 [/SUP], Allen C Cheng[SUP] 19 [/SUP], Peter Harcourt[SUP] 20 [/SUP], Patrick Clifton[SUP] 20 [/SUP], Jeremy Chase Crawford[SUP] 21 [/SUP], Paul G Thomas[SUP] 21 [/SUP], Adam K Wheatley[SUP] 22 [/SUP], Stephen J Kent[SUP] 23 [/SUP], Jamie Rossjohn[SUP] 24 [/SUP], Joseph Torresi[SUP] 1 [/SUP], Katherine Kedzierska[SUP] 25 [/SUP]
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[SUP]+[/SUP] T cells specific for SARS-CoV-2 epitopes in COVID-19 patients and unexposed individuals. Unlike CD8[SUP]+[/SUP] T cells directed toward subdominant epitopes (B7/N[SUB]257[/SUB], A2/S[SUB]269[/SUB], and A24/S[SUB]1,208[/SUB]) CD8[SUP]+[/SUP] T cells specific for the immunodominant B7/N[SUB]105[/SUB] 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[SUP]+[/SUP] 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/N[SUB]105[/SUB][SUP]+[/SUP]CD8[SUP]+[/SUP] T cells. Our study demonstrates high naive precursor frequency and TCR?? diversity within immunodominant B7/N[SUB]105[/SUB]-specific CD8[SUP]+[/SUP] 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.