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.

• MeSH
• COVID-19 imunologie   patofyziologie   MeSH
• genová knihovna MeSH
• imunologická paměť * MeSH
• lidé MeSH
• longitudinální studie MeSH
• mapování epitopu MeSH
• receptory antigenů T-buněk chemie   genetika   MeSH
• SARS-CoV-2 fyziologie   MeSH
• sekvence aminokyselin MeSH
• stupeň závažnosti nemoci MeSH
• T-lymfocyty imunologie   MeSH
• testování histokompatibility MeSH
• zkřížené reakce MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The diverse repertoire of T-cell receptors (TCR) plays a key role in the adaptive immune response to infections. Using TCR alpha and beta repertoire sequencing for T-cell subsets, as well as single-cell RNAseq and TCRseq, we track the concentrations and phenotypes of individual T-cell clones in response to primary and secondary yellow fever immunization - the model for acute infection in humans - showing their large diversity. We confirm the secondary response is an order of magnitude weaker, albeit ∼10 days faster than the primary one. Estimating the fraction of the T-cell response directed against the single immunodominant epitope, we identify the sequence features of TCRs that define the high precursor frequency of the two major TCR motifs specific for this particular epitope. We also show the consistency of clonal expansion dynamics between bulk alpha and beta repertoires, using a new methodology to reconstruct alpha-beta pairings from clonal trajectories.

• MeSH
• časové faktory MeSH
• dospělí MeSH
• epitopy imunologie   MeSH
• fenotyp MeSH
• imunologická paměť MeSH
• lidé MeSH
• podskupiny lymfocytů imunologie   fyziologie   MeSH
• receptory antigenů T-buněk genetika   imunologie   fyziologie   MeSH
• T-lymfocyty imunologie   fyziologie   virologie   MeSH
• transkriptom MeSH
• vakcína proti žluté zimnici imunologie   farmakologie   MeSH
• virus žluté zimnice imunologie   MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• žlutá zimnice imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH