Primary and secondary anti-viral response captured by the dynamics and phenotype of individual T cell clones

Anastasia A. Minervina, Mikhail V. Pogorelyy, Ekaterina A. Komech, Vadim K. Karnaukhov, Petra Bacher, Elisa Rosati, Andre Franke, Dmitriy M. Chudakov, Ilgar Z. Mamedov, Yury B. Lebedev, Thierry Mora, Aleksandra M. Walczak

    Research output: Contribution to journalArticlepeer-review

    24 Citations (Scopus)

    Abstract

    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 con1rm 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 de1ne the high precursor frequency of the two major TCR motifs speci1c 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.

    Original languageEnglish
    Article numbere53704
    JournaleLife
    Volume9
    DOIs
    Publication statusPublished - Feb 2020

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