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.

5 1 Kulakov National Medical Research Center for Obstetrics Gynecology and Perinatology Moscow Russian Federation

Center for Precision Genome Editing and Genetic Technologies for Biomedicine Pirogov Russian National Research Medical University Moscow Russian Federation

Center of Life Sciences Skoltech Moscow Russian Federation

Institute of Clinical Molecular Biology Kiel University Kiel Germany

Institute of Immunology Kiel University Kiel Germany

Laboratoire de physique de l'École normale supérieure ENS PSL Sorbonne Université Université de Paris and CNRS Paris France

Masaryk University Central European Institute of Technology Brno Czech Republic

Moscow State University Moscow Russian Federation

Shemyakin Ovchinnikov Institute of Bioorganic Chemistry Moscow Russian Federation

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