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. Mifsud; Denise 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

doi:10.1016/j.immuni.2021.04.009

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 journal › Article › peer-review

72 Scopus citations

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 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 language	English
Pages (from-to)	1066-1082.e5
Journal	Immunity
Volume	54
Issue number	5
DOIs	https://doi.org/10.1016/j.immuni.2021.04.009
State	Published - 11 May 2021

Keywords

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

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10.1016/j.immuni.2021.04.009

Cite this

Nguyen, T. H. O., Rowntree, L. C., Petersen, J., Chua, B. Y., Hensen, L., Kedzierski, L., van de Sandt, C. E., Chaurasia, P., Tan, H. X., Habel, J. R., Zhang, W., Allen, L. F., Earnest, L., Mak, K. Y., Juno, J. A., Wragg, K., Mordant, F. L., Amanat, F., Krammer, F., ... Kedzierska, K. (2021). CD8⁺ T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope display high naive precursor frequency and TCR promiscuity. Immunity, 54(5), 1066-1082.e5. https://doi.org/10.1016/j.immuni.2021.04.009

@article{3433e29c12604be39bb72925f6ec78f6,

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

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.",

keywords = "COVID-19, SARS-CoV-2-specific CD8+, T cells, TCR, immunodominant",

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

note = "Funding Information: We thank all the participants involved in the study, as well as Robyn Esterbauer, Hannah Kelly, Jane Batten, Helen Kent, and Kanta Subbarao for support with the cohorts and assays. We thank Jill Garlick, Janine Roney, Anne Paterson, and the research nurses at the Alfred Hospital. We acknowledge all DRASTIC (The use of cytokines as a preDictoR of disease Severity in criTically Ill Covid-patients) investigators from Austin Health and thank the participants involved. We thank Ana Copaescu for laboratory work and study coordination for the DRASTIC study. We thank Thomas Loudovaris and Stuart I. Mannering from St Vincent{\textquoteright}s Institute of Medical Research for access to spleen samples. This work was supported by the Clifford Craig Foundation to K.L.F. and K.K.; an NHMRC Leadership Investigator Grant to K.K. ( 1173871 ); an NHMRC Emerging Leadership Level 1 Investigator Grant to THON ( 1194036 ); an NHMRC program grant to D.L.D. ( 1132975 ); the Research Grants Council of the Hong Kong Special Administrative Region, China ( T11-712/19-N ) to K.K.; the Victorian government to S.J.K. and A.K.W.; an MRFF award ( 2002073 ) to S.J.K. and A.K.W.; an MRFF award ( 1202445 ) to K.K.; an MRFF award ( 2005544 ) to K.K., S.J.K., J.A.J., and A.K.W.; an NHMRC program grant ( 1149990 ) to S.J.K.; an NHMRC project grant ( 1162760 ) to A.K.W.; and NIH contract CIVR-HRP ( HHS-NIH-NIAID-BAA2018 ) to P.G.T. and K.K. A.K.W. is supported by an Emerging Leadership 1 Investigator Grant ( 1173433 ), J.A.J. by an NHMRC Early Career Fellowship (ECF) ( 1123673 ), D.L.D. by an NHMRC Principal Research Fellowship ( 1137285 ), and S.J.K. by an NHMRC Senior Principal Research Fellowship ( 1136322 ). C.E.S. has received funding from the European Union {\textquoteright}s Horizon 2020 research, innovation program under the Marie Sk{\l}odowska-Curie grant agreement ( 792532 ) and the Doherty Collaborative Seed Grant. J.R. is supported by an ARC Laureate fellowship. J.R.H. and W.Z. are supported by the Melbourne Research Scholarship from the University of Melbourne. L.H. is supported by the Melbourne International Research Scholarship (MIRS) and the Melbourne International Fee Remission Scholarship (MIFRS) from The University of Melbourne. J.C.C. and P.G.T. are supported by NIH NIAID ( R01 AI136514-03 ) and ALSAC at St. Jude. Funding Information: We thank all the participants involved in the study, as well as Robyn Esterbauer, Hannah Kelly, Jane Batten, Helen Kent, and Kanta Subbarao for support with the cohorts and assays. We thank Jill Garlick, Janine Roney, Anne Paterson, and the research nurses at the Alfred Hospital. We acknowledge all DRASTIC (The use of cytokines as a preDictoR of disease Severity in criTically Ill Covid-patients) investigators from Austin Health and thank the participants involved. We thank Ana Copaescu for laboratory work and study coordination for the DRASTIC study. We thank Thomas Loudovaris and Stuart I. Mannering from St Vincent's Institute of Medical Research for access to spleen samples. This work was supported by the Clifford Craig Foundation to K.L.F. and K.K.; an NHMRC Leadership Investigator Grant to K.K. (1173871); an NHMRC Emerging Leadership Level 1 Investigator Grant to THON (1194036); an NHMRC program grant to D.L.D. (1132975); the Research Grants Council of the Hong Kong Special Administrative Region, China (T11-712/19-N) to K.K.; the Victorian government to S.J.K. and A.K.W.; an MRFF award (2002073) to S.J.K. and A.K.W.; an MRFF award (1202445) to K.K.; an MRFF award (2005544) to K.K. S.J.K. J.A.J. and A.K.W.; an NHMRC program grant (1149990) to S.J.K.; an NHMRC project grant (1162760) to A.K.W.; and NIH contract CIVR-HRP (HHS-NIH-NIAID-BAA2018) to P.G.T. and K.K. A.K.W. is supported by an Emerging Leadership 1 Investigator Grant (1173433), J.A.J. by an NHMRC Early Career Fellowship (ECF) (1123673), D.L.D. by an NHMRC Principal Research Fellowship (1137285), and S.J.K. by an NHMRC Senior Principal Research Fellowship (1136322). C.E.S. has received funding from the European Union's Horizon 2020 research, innovation program under the Marie Sk?odowska-Curie grant agreement (792532) and the Doherty Collaborative Seed Grant. J.R. is supported by an ARC Laureate fellowship. J.R.H. and W.Z. are supported by the Melbourne Research Scholarship from the University of Melbourne. L.H. is supported by the Melbourne International Research Scholarship (MIRS) and the Melbourne International Fee Remission Scholarship (MIFRS) from The University of Melbourne. J.C.C. and P.G.T. are supported by NIH NIAID (R01 AI136514-03) and ALSAC at St. Jude. K.K. led the study. K.K. J.T. and J.R. supervised the study. K.K. J.T. J.R. T.H.O.N. L.C.R. J.P. B.Y.C. and L.K. designed the experiments. T.H.O.N. L.C.R. J.P. B.Y.C. L.H. L.K. P.C. H.T. J.R.H. W.Z. L.A. L.E. K.Y.M. J.A.J. K.W. F.L.M. and A.K.W. performed and analyzed experiments. F.A. F.K. N.A.M. and A.K.W. provided reagents. D.L.D. K.L.F. S.S. J.K. L.M.W. G.P.W. F.J. E.M. C.L.G. N.E.H. O.C.S. J.A.T. A.C.C. P.H. P.C. and S.J.K. recruited the patient cohorts. T.H.O.N. L.C.R. J.P. J.R. J.T. and K.K. provided intellectual input into the study design and data interpretation. T.H.O.N. L.C.R. C.E.S. J.C.C. and P.G.T. analyzed TCR sequences. T.H.O.N. L.C.R. and K.K. wrote the manuscript. All authors reviewed and approved the manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",

year = "2021",

month = may,

day = "11",

doi = "10.1016/j.immuni.2021.04.009",

language = "English",

volume = "54",

pages = "1066--1082.e5",

journal = "Immunity",

issn = "1074-7613",

publisher = "Cell Press",

number = "5",

}

Nguyen, THO, Rowntree, LC, Petersen, J, Chua, BY, Hensen, L, Kedzierski, L, van de Sandt, CE, Chaurasia, P, Tan, HX, Habel, JR, Zhang, W, Allen, LF, Earnest, L, Mak, KY, Juno, JA, Wragg, K, Mordant, FL, Amanat, F, Krammer, F, Mifsud, NA, Doolan, DL, Flanagan, KL, Sonda, S, Kaur, J, 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 2021, 'CD8⁺ T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope display high naive precursor frequency and TCR promiscuity', Immunity, vol. 54, no. 5, pp. 1066-1082.e5. https://doi.org/10.1016/j.immuni.2021.04.009

TY - JOUR

T1 - CD8+ T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope display high naive precursor frequency and TCR promiscuity

AU - Nguyen, Thi H.O.

AU - Rowntree, Louise C.

AU - Petersen, Jan

AU - Chua, Brendon Y.

AU - Hensen, Luca

AU - Kedzierski, Lukasz

AU - van de Sandt, Carolien E.

AU - Chaurasia, Priyanka

AU - Tan, Hyon Xhi

AU - Habel, Jennifer R.

AU - Zhang, Wuji

AU - Allen, Lilith F.

AU - Earnest, Linda

AU - Mak, Kai Yan

AU - Juno, Jennifer A.

AU - Wragg, Kathleen

AU - Mordant, Francesca L.

AU - Amanat, Fatima

AU - Krammer, Florian

AU - Mifsud, Nicole A.

AU - Doolan, Denise L.

AU - Flanagan, Katie L.

AU - Sonda, Sabrina

AU - Kaur, Jasveen

AU - Wakim, Linda M.

AU - Westall, Glen P.

AU - James, Fiona

AU - Mouhtouris, Effie

AU - Gordon, Claire L.

AU - Holmes, Natasha E.

AU - Smibert, Olivia C.

AU - Trubiano, Jason A.

AU - Cheng, Allen C.

AU - Harcourt, Peter

AU - Clifton, Patrick

AU - Crawford, Jeremy Chase

AU - Thomas, Paul G.

AU - Wheatley, Adam K.

AU - Kent, Stephen J.

AU - Rossjohn, Jamie

AU - Torresi, Joseph

AU - Kedzierska, Katherine

N1 - Funding Information: We thank all the participants involved in the study, as well as Robyn Esterbauer, Hannah Kelly, Jane Batten, Helen Kent, and Kanta Subbarao for support with the cohorts and assays. We thank Jill Garlick, Janine Roney, Anne Paterson, and the research nurses at the Alfred Hospital. We acknowledge all DRASTIC (The use of cytokines as a preDictoR of disease Severity in criTically Ill Covid-patients) investigators from Austin Health and thank the participants involved. We thank Ana Copaescu for laboratory work and study coordination for the DRASTIC study. We thank Thomas Loudovaris and Stuart I. Mannering from St Vincent’s Institute of Medical Research for access to spleen samples. This work was supported by the Clifford Craig Foundation to K.L.F. and K.K.; an NHMRC Leadership Investigator Grant to K.K. ( 1173871 ); an NHMRC Emerging Leadership Level 1 Investigator Grant to THON ( 1194036 ); an NHMRC program grant to D.L.D. ( 1132975 ); the Research Grants Council of the Hong Kong Special Administrative Region, China ( T11-712/19-N ) to K.K.; the Victorian government to S.J.K. and A.K.W.; an MRFF award ( 2002073 ) to S.J.K. and A.K.W.; an MRFF award ( 1202445 ) to K.K.; an MRFF award ( 2005544 ) to K.K., S.J.K., J.A.J., and A.K.W.; an NHMRC program grant ( 1149990 ) to S.J.K.; an NHMRC project grant ( 1162760 ) to A.K.W.; and NIH contract CIVR-HRP ( HHS-NIH-NIAID-BAA2018 ) to P.G.T. and K.K. A.K.W. is supported by an Emerging Leadership 1 Investigator Grant ( 1173433 ), J.A.J. by an NHMRC Early Career Fellowship (ECF) ( 1123673 ), D.L.D. by an NHMRC Principal Research Fellowship ( 1137285 ), and S.J.K. by an NHMRC Senior Principal Research Fellowship ( 1136322 ). C.E.S. has received funding from the European Union ’s Horizon 2020 research, innovation program under the Marie Skłodowska-Curie grant agreement ( 792532 ) and the Doherty Collaborative Seed Grant. J.R. is supported by an ARC Laureate fellowship. J.R.H. and W.Z. are supported by the Melbourne Research Scholarship from the University of Melbourne. L.H. is supported by the Melbourne International Research Scholarship (MIRS) and the Melbourne International Fee Remission Scholarship (MIFRS) from The University of Melbourne. J.C.C. and P.G.T. are supported by NIH NIAID ( R01 AI136514-03 ) and ALSAC at St. Jude. Funding Information: We thank all the participants involved in the study, as well as Robyn Esterbauer, Hannah Kelly, Jane Batten, Helen Kent, and Kanta Subbarao for support with the cohorts and assays. We thank Jill Garlick, Janine Roney, Anne Paterson, and the research nurses at the Alfred Hospital. We acknowledge all DRASTIC (The use of cytokines as a preDictoR of disease Severity in criTically Ill Covid-patients) investigators from Austin Health and thank the participants involved. We thank Ana Copaescu for laboratory work and study coordination for the DRASTIC study. We thank Thomas Loudovaris and Stuart I. Mannering from St Vincent's Institute of Medical Research for access to spleen samples. This work was supported by the Clifford Craig Foundation to K.L.F. and K.K.; an NHMRC Leadership Investigator Grant to K.K. (1173871); an NHMRC Emerging Leadership Level 1 Investigator Grant to THON (1194036); an NHMRC program grant to D.L.D. (1132975); the Research Grants Council of the Hong Kong Special Administrative Region, China (T11-712/19-N) to K.K.; the Victorian government to S.J.K. and A.K.W.; an MRFF award (2002073) to S.J.K. and A.K.W.; an MRFF award (1202445) to K.K.; an MRFF award (2005544) to K.K. S.J.K. J.A.J. and A.K.W.; an NHMRC program grant (1149990) to S.J.K.; an NHMRC project grant (1162760) to A.K.W.; and NIH contract CIVR-HRP (HHS-NIH-NIAID-BAA2018) to P.G.T. and K.K. A.K.W. is supported by an Emerging Leadership 1 Investigator Grant (1173433), J.A.J. by an NHMRC Early Career Fellowship (ECF) (1123673), D.L.D. by an NHMRC Principal Research Fellowship (1137285), and S.J.K. by an NHMRC Senior Principal Research Fellowship (1136322). C.E.S. has received funding from the European Union's Horizon 2020 research, innovation program under the Marie Sk?odowska-Curie grant agreement (792532) and the Doherty Collaborative Seed Grant. J.R. is supported by an ARC Laureate fellowship. J.R.H. and W.Z. are supported by the Melbourne Research Scholarship from the University of Melbourne. L.H. is supported by the Melbourne International Research Scholarship (MIRS) and the Melbourne International Fee Remission Scholarship (MIFRS) from The University of Melbourne. J.C.C. and P.G.T. are supported by NIH NIAID (R01 AI136514-03) and ALSAC at St. Jude. K.K. led the study. K.K. J.T. and J.R. supervised the study. K.K. J.T. J.R. T.H.O.N. L.C.R. J.P. B.Y.C. and L.K. designed the experiments. T.H.O.N. L.C.R. J.P. B.Y.C. L.H. L.K. P.C. H.T. J.R.H. W.Z. L.A. L.E. K.Y.M. J.A.J. K.W. F.L.M. and A.K.W. performed and analyzed experiments. F.A. F.K. N.A.M. and A.K.W. provided reagents. D.L.D. K.L.F. S.S. J.K. L.M.W. G.P.W. F.J. E.M. C.L.G. N.E.H. O.C.S. J.A.T. A.C.C. P.H. P.C. and S.J.K. recruited the patient cohorts. T.H.O.N. L.C.R. J.P. J.R. J.T. and K.K. provided intellectual input into the study design and data interpretation. T.H.O.N. L.C.R. C.E.S. J.C.C. and P.G.T. analyzed TCR sequences. T.H.O.N. L.C.R. and K.K. wrote the manuscript. All authors reviewed and approved the manuscript. The authors declare no competing interests. Publisher Copyright: © 2021 Elsevier Inc.

PY - 2021/5/11

Y1 - 2021/5/11

N2 - 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.

AB - 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.

KW - COVID-19

KW - SARS-CoV-2-specific CD8+

KW - T cells

KW - TCR

KW - immunodominant

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U2 - 10.1016/j.immuni.2021.04.009

DO - 10.1016/j.immuni.2021.04.009

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AN - SCOPUS:85105283794

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