Recruitment of highly cytotoxic CD8+ T cell receptors in mild SARS-CoV-2 infection

Karolin I. Wagner; Laura M. Mateyka; Sebastian Jarosch; Vincent Grass; Simone Weber; Kilian Schober; Monika Hammel; Teresa Burrell; Behnam Kalali; Holger Poppert; Henriette Beyer; Sophia Schambeck; Stefan Holdenrieder; Andrea Strötges-Achatz; Verena Haselmann; Michael Neumaier; Johanna Erber; Alina Priller; Sarah Yazici; Hedwig Roggendorf; Marcus Odendahl; Torsten Tonn; Andrea Dick; Klaus Witter; Hrvoje Mijočević; Ulrike Protzer; Percy A. Knolle; Andreas Pichlmair; Claudia S. Crowell; Markus Gerhard; Elvira D'Ippolito; Dirk H. Busch

doi:10.1016/j.celrep.2021.110214

Recruitment of highly cytotoxic CD8⁺ T cell receptors in mild SARS-CoV-2 infection

Karolin I. Wagner
, Laura M. Mateyka
, Sebastian Jarosch
, Vincent Grass
, Simone Weber
, Kilian Schober
, Monika Hammel
, Teresa Burrell
, Behnam Kalali
, Holger Poppert
, Henriette Beyer
, Sophia Schambeck
, Stefan Holdenrieder
, Andrea Strötges-Achatz
, Verena Haselmann
, Michael Neumaier
, Johanna Erber
, Alina Priller
, Sarah Yazici
, Hedwig Roggendorf

Marcus Odendahl, Torsten Tonn, Andrea Dick, Klaus Witter, Hrvoje Mijočević, Ulrike Protzer, Percy A. Knolle, Andreas Pichlmair, Claudia S. Crowell, Markus Gerhard, Elvira D'Ippolito, Dirk H. Busch

Technical University of Munich
Universitätsklinikum Erlangen
Helios Klinikum München West
Heidelberg University
Technischen Universität Dresden
Ludwig-Maximilians-Universität München
Partner Site Munich

Research output: Contribution to journal › Article › peer-review

38 Scopus citations

Abstract

T cell immunity is crucial for control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and has been studied widely on a quantitative level. However, the quality of responses, in particular of CD8⁺ T cells, has only been investigated marginally so far. Here, we isolate T cell receptor (TCR) repertoires specific for immunodominant SARS-CoV-2 epitopes restricted to common human Leukocyte antigen (HLA) class I molecules in convalescent individuals. SARS-CoV-2-specific CD8⁺ T cells are detected up to 12 months after infection. TCR repertoires are diverse, with heterogeneous functional avidity and cytotoxicity toward virus-infected cells, as demonstrated for TCR-engineered T cells. High TCR functionality correlates with gene signatures that, remarkably, could be retrieved for each epitope:HLA combination analyzed. Overall, our data demonstrate that polyclonal and highly functional CD8⁺ TCRs—classic features of protective immunity—are recruited upon mild SARS-CoV-2 infection, providing tools to assess the quality of and potentially restore functional CD8⁺ T cell immunity.

Original language	English
Article number	110214
Journal	Cell Reports
Volume	38
Issue number	2
DOIs	https://doi.org/10.1016/j.celrep.2021.110214
State	Published - 11 Jan 2022

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

CD8 T cells
SARS-CoV-2 infection
T cell immunity
T cell receptor
TCR engineering
TCR identification
cytotoxic T cells
mild COVID-19
scRNA sequencing

Access to Document

10.1016/j.celrep.2021.110214

Cite this

Wagner, K. I., Mateyka, L. M., Jarosch, S., Grass, V., Weber, S., Schober, K., Hammel, M., Burrell, T., Kalali, B., Poppert, H., Beyer, H., Schambeck, S., Holdenrieder, S., Strötges-Achatz, A., Haselmann, V., Neumaier, M., Erber, J., Priller, A., Yazici, S., ... Busch, D. H. (2022). Recruitment of highly cytotoxic CD8⁺ T cell receptors in mild SARS-CoV-2 infection. Cell Reports, 38(2), Article 110214. https://doi.org/10.1016/j.celrep.2021.110214

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title = "Recruitment of highly cytotoxic CD8+ T cell receptors in mild SARS-CoV-2 infection",

abstract = "T cell immunity is crucial for control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and has been studied widely on a quantitative level. However, the quality of responses, in particular of CD8+ T cells, has only been investigated marginally so far. Here, we isolate T cell receptor (TCR) repertoires specific for immunodominant SARS-CoV-2 epitopes restricted to common human Leukocyte antigen (HLA) class I molecules in convalescent individuals. SARS-CoV-2-specific CD8+ T cells are detected up to 12 months after infection. TCR repertoires are diverse, with heterogeneous functional avidity and cytotoxicity toward virus-infected cells, as demonstrated for TCR-engineered T cells. High TCR functionality correlates with gene signatures that, remarkably, could be retrieved for each epitope:HLA combination analyzed. Overall, our data demonstrate that polyclonal and highly functional CD8+ TCRs{\textemdash}classic features of protective immunity{\textemdash}are recruited upon mild SARS-CoV-2 infection, providing tools to assess the quality of and potentially restore functional CD8+ T cell immunity.",

keywords = "CD8 T cells, SARS-CoV-2 infection, T cell immunity, T cell receptor, TCR engineering, TCR identification, cytotoxic T cells, mild COVID-19, scRNA sequencing",

author = "Wagner, \{Karolin I.\} and Mateyka, \{Laura M.\} and Sebastian Jarosch and Vincent Grass and Simone Weber and Kilian Schober and Monika Hammel and Teresa Burrell and Behnam Kalali and Holger Poppert and Henriette Beyer and Sophia Schambeck and Stefan Holdenrieder and Andrea Str{\"o}tges-Achatz and Verena Haselmann and Michael Neumaier and Johanna Erber and Alina Priller and Sarah Yazici and Hedwig Roggendorf and Marcus Odendahl and Torsten Tonn and Andrea Dick and Klaus Witter and Hrvoje Mijo{\v c}evi{\'c} and Ulrike Protzer and Knolle, \{Percy A.\} and Andreas Pichlmair and Crowell, \{Claudia S.\} and Markus Gerhard and Elvira D'Ippolito and Busch, \{Dirk H.\}",

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year = "2022",

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doi = "10.1016/j.celrep.2021.110214",

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Wagner, KI, Mateyka, LM, Jarosch, S, Grass, V, Weber, S, Schober, K, Hammel, M, Burrell, T, Kalali, B, Poppert, H, Beyer, H, Schambeck, S, Holdenrieder, S, Strötges-Achatz, A, Haselmann, V, Neumaier, M, Erber, J, Priller, A, Yazici, S, Roggendorf, H, Odendahl, M, Tonn, T, Dick, A, Witter, K, Mijočević, H, Protzer, U , Knolle, PA , Pichlmair, A, Crowell, CS, Gerhard, M, D'Ippolito, E & Busch, DH 2022, 'Recruitment of highly cytotoxic CD8⁺ T cell receptors in mild SARS-CoV-2 infection', Cell Reports, vol. 38, no. 2, 110214. https://doi.org/10.1016/j.celrep.2021.110214

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AU - Wagner, Karolin I.

AU - Mateyka, Laura M.

AU - Jarosch, Sebastian

AU - Grass, Vincent

AU - Weber, Simone

AU - Schober, Kilian

AU - Hammel, Monika

AU - Burrell, Teresa

AU - Kalali, Behnam

AU - Poppert, Holger

AU - Beyer, Henriette

AU - Schambeck, Sophia

AU - Holdenrieder, Stefan

AU - Strötges-Achatz, Andrea

AU - Haselmann, Verena

AU - Neumaier, Michael

AU - Erber, Johanna

AU - Priller, Alina

AU - Yazici, Sarah

AU - Roggendorf, Hedwig

AU - Odendahl, Marcus

AU - Tonn, Torsten

AU - Dick, Andrea

AU - Witter, Klaus

AU - Mijočević, Hrvoje

AU - Protzer, Ulrike

AU - Knolle, Percy A.

AU - Pichlmair, Andreas

AU - Crowell, Claudia S.

AU - Gerhard, Markus

AU - D'Ippolito, Elvira

AU - Busch, Dirk H.

PY - 2022/1/11

Y1 - 2022/1/11

N2 - T cell immunity is crucial for control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and has been studied widely on a quantitative level. However, the quality of responses, in particular of CD8+ T cells, has only been investigated marginally so far. Here, we isolate T cell receptor (TCR) repertoires specific for immunodominant SARS-CoV-2 epitopes restricted to common human Leukocyte antigen (HLA) class I molecules in convalescent individuals. SARS-CoV-2-specific CD8+ T cells are detected up to 12 months after infection. TCR repertoires are diverse, with heterogeneous functional avidity and cytotoxicity toward virus-infected cells, as demonstrated for TCR-engineered T cells. High TCR functionality correlates with gene signatures that, remarkably, could be retrieved for each epitope:HLA combination analyzed. Overall, our data demonstrate that polyclonal and highly functional CD8+ TCRs—classic features of protective immunity—are recruited upon mild SARS-CoV-2 infection, providing tools to assess the quality of and potentially restore functional CD8+ T cell immunity.

AB - T cell immunity is crucial for control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and has been studied widely on a quantitative level. However, the quality of responses, in particular of CD8+ T cells, has only been investigated marginally so far. Here, we isolate T cell receptor (TCR) repertoires specific for immunodominant SARS-CoV-2 epitopes restricted to common human Leukocyte antigen (HLA) class I molecules in convalescent individuals. SARS-CoV-2-specific CD8+ T cells are detected up to 12 months after infection. TCR repertoires are diverse, with heterogeneous functional avidity and cytotoxicity toward virus-infected cells, as demonstrated for TCR-engineered T cells. High TCR functionality correlates with gene signatures that, remarkably, could be retrieved for each epitope:HLA combination analyzed. Overall, our data demonstrate that polyclonal and highly functional CD8+ TCRs—classic features of protective immunity—are recruited upon mild SARS-CoV-2 infection, providing tools to assess the quality of and potentially restore functional CD8+ T cell immunity.

KW - CD8 T cells

KW - SARS-CoV-2 infection

KW - T cell immunity

KW - T cell receptor

KW - TCR engineering

KW - TCR identification

KW - cytotoxic T cells

KW - mild COVID-19

KW - scRNA sequencing

UR - https://www.scopus.com/pages/publications/85121976832

U2 - 10.1016/j.celrep.2021.110214

DO - 10.1016/j.celrep.2021.110214

M3 - Article

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AN - SCOPUS:85121976832

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