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arXiv · 2005.08290

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
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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.

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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. 2020-09-30. Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T cell memory formation after mild COVID-19 infection. https://doi.org/10.7554/elife.63502

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