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

• DOI: 10.7554/elife.63502
• Publication Date: 2021-01-05T13:03:18Z
• Authors: Anastasia A Miner...; Ekaterina A Komech; Aleksei Titov; Meriem Bensouda K...; Elisa Rosati; Ilgar Z Mamedov; Andre Franke; Grigory A Efimov; Dmitriy M Chudakov; Thierry Mora; Aleksandra M Walczak; Yuri B Lebedev; Mikhail V Pogorelyy
• Keywords: Male; 0301 basic medicine; QH301-705.5; [SDV]Life Sciences [q-bio]; Science; T-Lymphocytes; Receptors, Antigen, T-Cell; Cross Reactions; Severity of Illness Index; 03 medical and health sciences; Humans; Quantitative Biology - Genomics; Amino Acid Sequence; Longitudinal Studies; Biology (General); Gene Library; [PHYS]Physics [physics]; Genomics (q-bio.GN); RepSeq; SARS-CoV-2; Histocompatibility Testing; Q; R; COVID-19; 3. Good health; FOS: Biological sciences; Medicine; Female; Immunologic Memory; TCR; Epitope Mapping; Computational and Systems Biology

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 is 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. We describe characteristic motifs in TCR sequences of COVID-19-reactive clones and show preferential occurrence 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 time point, suggesting participation of pre-existing cross-reactive memory T cells in the immune response to SARS-CoV-2.