Tweet
Elife
. 2021 Jan 5;10:e63502.
doi: 10.7554/eLife.63502. Online ahead of print.
Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T cell memory formation after mild COVID-19 infection
Anastasia A Minervina 1 , Ekaterina A Komech 1 , Aleksei Titov 2 , Meriem Bensouda Koraichi 3 , Elisa Rosati 4 , Ilgar Z Mamedov 1 , Andre Franke 4 , Grigory A Efimov 2 , Dmitriy M Chudakov 1 , Thierry Mora 5 , Aleksandra M Walczak 3 , Yuri B Lebedev 1 , Mikhail V Pogorelyy 1
Affiliations
- PMID: 33399535
- DOI: 10.7554/eLife.63502
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.
Keywords: computational biology; human; immunology; inflammation; systems biology.