Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T cell memory formation after mild COVID-19 infection
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Federation
- National Research Center for Hematology, Russian Federation
- École Normale Supérieure, France
- Kiel University, Germany
- Ecole Normale Supérieure de Paris, France
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.
Data availability
Raw sequencing data are deposited to the Short Read Archive (SRA) accession: PRJNA633317. Resulting repertoires of SARS-CoV-2-reactive clones can be found in SI Tables 3-6 and also accessed from: https://github.com/pogorely/Minervina_COVID Processed TCRalpha and TCRbeta repertoire datasets are available at : https://zenodo.org/record/3835955
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A large-scale database of T-cell receptor beta (TCRb) sequences and binding associations from natural and synthetic exposure to SARS-CoV-2ImmuneAccess, DOI: https://doi.org/10.21417/ADPT2020COVID.
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Immunosequencing identifies signatures of cytomegalovirus exposure history and HLA-mediated effects on the T-cell repertoireImmuneAccess, DOI: https://doi.org/10.21417/B7001Z.
Article and author information
Author details
Anastasia A Minervina
Dmitriy M Chudakov
Aleksandra M Walczak
Mikhail V Pogorelyy
Funding
Russian Science Foundation (RSF 20-15-00351)
- Yuri B Lebedev
Deutsche Forschungsgemeinschaft (Exc2167)
- Andre Franke
Deutsche Forschungsgemeinschaft (4096610003)
- Andre Franke
H2020 European Research Council (COG 724208)
- Aleksandra M Walczak
Russian Foundation for Basic Research (19-54-12-011)
- Ilgar Z Mamedov
Russian Foundation for Basic Research (18-19-09132)
- Ilgar Z Mamedov
Ministry of Science and Higher Education of the Russian Federation (075-15-2019-1789)
- Dmitriy M Chudakov
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: All subjects gave written informed consent in accordance with the Declaration of Helsinki. The study protocol was approved by the Pirogov Russian National Research Medical University local ethics committee (#194 granted on March 16, 2020)
Copyright
© 2021, Minervina et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T cell memory formation after mild COVID-19 infection
eLife 10:e63502.
https://doi.org/10.7554/eLife.63502
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