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

Minervina, Anastasia A.; Komech, Ekaterina A.; Titov, Aleksei; Koraichi, Meriem Bensouda; Rosati, Elisa; Mamedov, Ilgar Z.; Franke, Andre; Efimov, Grigory A.; Chudakov, Dmitriy M.; Mora, Thierry; Walczak, Aleksandra M.; Lebedev, Yuri B.; Pogorelyy, Mikhail V.

COVID-19 is a global pandemic caused by the SARS-CoV-2 coronavirus. The T cell response is a critical part of both individual and herd immunity to SARS-CoV-2 and the efficacy of developed vaccines. 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 sequencing to track changes in the T cell repertoire following two mild cases of COVID-19 infection. In both donors we identified SARS-CoV-2-responding CD4+ and CD8+ T cell clones. We describe characteristic motifs in TCR sequences of COVID-19-reactive clones, suggesting the existence of immunodominant epitopes. We show that in both donors the majority of infection-reactive clonotypes acquire memory phenotypes. Certain CD4+ 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.