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.
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
Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T cell memory formation after mild COVID-19 infectionZenodo DOI:10.5281/zenodo.3835955.
Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T cell memory formation after mild COVID-19 infectionNCBI Short Read Archive, PRJNA633317.
Comprehensive analysis of antiviral adaptive immunity formation and reactivation down to single cell levelNCBI Short Read Archive, PRJNA577794.
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.
Immunosequencing identifies signatures of cytomegalovirus exposure history and HLA-mediated effects on the T-cell repertoireImmuneAccess, DOI: https://doi.org/10.21417/B7001Z.
- Yuri B Lebedev
- Andre Franke
- Andre Franke
- Aleksandra M Walczak
- Ilgar Z Mamedov
- Ilgar Z Mamedov
- Dmitriy M Chudakov
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
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)
- Sandeep Krishna, National Centre for Biological Sciences‐Tata Institute of Fundamental Research, India
© 2021, Minervina et al.
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