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Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T cell memory formation after mild COVID-19 infection

Anastasia A. Minervina, Ekaterina A. Komech, Aleksei Titov, Meriem Bensouda Koraichi, Elisa Rosati, Ilgar Z. Mamedov, Andre Franke, Grigory A. Efimov, Dmitriy M. Chudakov, View ORCID ProfileThierry Mora, Aleksandra M. Walczak, Yuri B. Lebedev, Mikhail V. Pogorelyy
doi: https://doi.org/10.1101/2020.05.18.100545
Anastasia A. Minervina
1Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia
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Ekaterina A. Komech
1Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia
2Pirogov Russian National Research Medical University, Moscow, Russia
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Aleksei Titov
3National Research Center for Hematology, Moscow, Russia
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Meriem Bensouda Koraichi
4Laboratoire de physique de l’École normale supérieure, ENS, PSL, Sorbonne Université, Université de Paris, and CNRS, Paris, France
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Elisa Rosati
5Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany
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Ilgar Z. Mamedov
1Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia
2Pirogov Russian National Research Medical University, Moscow, Russia
6Masaryk University, Central European Institute of Technology, Brno, Czech Republic
7V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia
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Andre Franke
5Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany
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Grigory A. Efimov
3National Research Center for Hematology, Moscow, Russia
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Dmitriy M. Chudakov
1Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia
2Pirogov Russian National Research Medical University, Moscow, Russia
6Masaryk University, Central European Institute of Technology, Brno, Czech Republic
8Center of Life Sciences, Skoltech, Moscow, Russia
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Thierry Mora
4Laboratoire de physique de l’École normale supérieure, ENS, PSL, Sorbonne Université, Université de Paris, and CNRS, Paris, France
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  • ORCID record for Thierry Mora
  • For correspondence: tmora@lps.ens.fr
Aleksandra M. Walczak
4Laboratoire de physique de l’École normale supérieure, ENS, PSL, Sorbonne Université, Université de Paris, and CNRS, Paris, France
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Yuri B. Lebedev
1Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia
9Moscow State University, Moscow, Russia
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Mikhail V. Pogorelyy
1Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia
2Pirogov Russian National Research Medical University, Moscow, Russia
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Abstract

COVID-19 is a global pandemic caused by the SARS-CoV-2 coronavirus. T cells play a key role in the adaptive antiviral immune response by killing infected cells and facilitating the selection of virus-specific antibodies. However neither the dynamics and cross-reactivity of the SARS-CoV-2-specific T cell response nor the diversity of resulting immune memory are well understood. In this study we use longitudinal high-throughput T cell receptor (TCR) sequencing to track changes in the T cell repertoire following two mild cases of COVID-19. In both donors we identified CD4+ and CD8+ T cell clones with transient clonal expansion after infection. The antigen specificity of CD8+ TCR sequences to SARS-CoV-2 epitopes was confirmed by both MHC tetramer binding and presence in large database of SARS-CoV-2 epitope-specific TCRs. We describe characteristic motifs in TCR sequences of COVID-19-reactive clones and show preferential occurence of these motifs in publicly available large dataset of repertoires from COVID-19 patients. We show that in both donors the majority of infection-reactive clonotypes acquire memory phenotypes. Certain T cell clones were detected in the memory fraction at the pre-infection timepoint, suggesting participation of pre-existing cross-reactive memory T cells in the immune response to SARS-CoV-2.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://github.com/pogorely/Minervina_COVID

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted October 01, 2020.
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Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T cell memory formation after mild COVID-19 infection
Anastasia A. Minervina, Ekaterina A. Komech, Aleksei Titov, Meriem Bensouda Koraichi, Elisa Rosati, Ilgar Z. Mamedov, Andre Franke, Grigory A. Efimov, Dmitriy M. Chudakov, Thierry Mora, Aleksandra M. Walczak, Yuri B. Lebedev, Mikhail V. Pogorelyy
bioRxiv 2020.05.18.100545; doi: https://doi.org/10.1101/2020.05.18.100545
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Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T cell memory formation after mild COVID-19 infection
Anastasia A. Minervina, Ekaterina A. Komech, Aleksei Titov, Meriem Bensouda Koraichi, Elisa Rosati, Ilgar Z. Mamedov, Andre Franke, Grigory A. Efimov, Dmitriy M. Chudakov, Thierry Mora, Aleksandra M. Walczak, Yuri B. Lebedev, Mikhail V. Pogorelyy
bioRxiv 2020.05.18.100545; doi: https://doi.org/10.1101/2020.05.18.100545

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