SARS-CoV-2 hybrid immunity is more protective than vaccination or prior infection alone. To investigate the kinetics of spike (S) reactive T cells (T S}) from SARS-CoV-2 infection through mRNA vaccination in persons with hybrid immunity, we identified the T cell receptor (TCR) sequences of thousands of index T S} cells and tracked their frequency in bulk TCRβ repertoires sampled longitudinally from the peripheral blood of recovered COVID-19 patients. Vaccinations led to large expansions in memory T S} cell clonotypes, the majority of which were CD8^{+} T cells, while also eliciting diverse T S} cell clonotypes not observed prior to vaccination. TCR sequence similarity clustering identified public CD8^{+} and CD4^{+} TCR motifs associated with S-specificity. Synthesis of longitudinal bulk ex vivo single-chain TCRβ repertoires and paired-chain TCRɑβ sequences from droplet sequencing of T S} cells provides a roadmap for rapid assessment of T cell responses to vaccines and emerging pathogens.
【저자키워드】 SARS-CoV-2, mRNA vaccine, T cell receptor, immune repertoire, Clustering analysis,