Precise tracking of vaccine-responding T cell clones reveals convergent and personalized response in identical twins

Pogorelyy, Mikhail V.; Minervina, Anastasia A.; Touzel, Maximilian Puelma; Sycheva, Anastasiia L.; Komech, Ekaterina A.; Kovalenko, Elena I.; Karganova, Galina G.; Egorov, Evgeniy S.; Komkov, Alexander; Chudakov, Dmitriy M.; Mamedov, Ilgar Z.; Mora, Thierry; Walczak, Aleksandra M.; Lebedev, Yuri B.

doi:10.1073/pnas.1809642115

Cited by 117 publications

(217 citation statements)

References 45 publications

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“…In the recent study, each donor responded to the vaccine with ~1000 different clonotypes corresponding to both cytotoxic and helper T‐cells , with dynamics similar to those observed in previous studies using MHC‐multimer and T‐cell activation marker staining . The specificity of a substantial fraction of the HTS‐identified YF‐responding clonotypes was confirmed by independent assays . In another study, Qi et al .…”

Section: Clonal Tracking In Timesupporting

confidence: 76%

“…However, the pre‐challenge timepoint is needed for clonal expansion identification. In YF‐vaccination study contraction dynamics from the peak of the response to the later timepoint was used to overcome this challenge. In general, strong clonal expansion in tissue of interest is needed to identify disease‐associated clonotypes using this approach.…”

Section: Clonal Tracking In Timementioning

confidence: 99%

“…Second, for some epitopes there might be few or no public sequences . In the majority of cases, antigen‐specific clones are unique to a single donor, with little sharing observed even between genetically identical twins .…”

Section: Clonal Sharingmentioning

confidence: 99%

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T‐cell receptor and B‐cell receptor repertoire profiling in adaptive immunity

2019

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Summary B‐cell receptors and T‐cell receptors are the key molecules responsible for specific antigen recognition in adaptive immunity. The huge diversity of immune receptor repertoires constrained their comprehensive studies in the past. More recently, however, high‐throughput sequencing based techniques have revolutionized the field of immune receptor repertoire profiling enabling new insights into the development and function of the adaptive immune system. In this review we describe current methods for immune receptor profiling and software tools used for repertoire reconstruction from raw sequencing data. We also provide examples of how immune repertoire profiling can be used to study adaptive immunity in disease and in the course of organ and bone marrow transplantation.

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Section: Clonal Tracking In Timesupporting

confidence: 76%

Section: Clonal Tracking In Timementioning

confidence: 99%

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T‐cell receptor and B‐cell receptor repertoire profiling in adaptive immunity

2019

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“…Yellow fever vaccine is a live attenuated virus with a peak of viremia happening around day 7 after vaccine administration [2][3][4]. The dynamics of primary T-cell response was investigated by various techniques: cell activation marker staining [2,[5][6][7], MHC multimer staining [3,5,7,8], high-throughput sequencing [9,10] and deuterium cell labelling [11]. Primary T-cell response sharply peaks around 2 weeks after YFV17D (vaccine strain of yellow fever virus) vaccination [2,3,6,8,10].…”

Section: Introductionmentioning

confidence: 99%

“…The dynamics of primary T-cell response was investigated by various techniques: cell activation marker staining [2,[5][6][7], MHC multimer staining [3,5,7,8], high-throughput sequencing [9,10] and deuterium cell labelling [11]. Primary T-cell response sharply peaks around 2 weeks after YFV17D (vaccine strain of yellow fever virus) vaccination [2,3,6,8,10]. The immune response is very diverse and targets multiple epitopes inside the YF virus [3,5,8,12,13].…”

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of antiviral adaptive immunity formation and reactivation down to single-cell level

Minervina

Pogorelyy

Komech

et al. 2019

Preprint

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These authors contributed equally.The diverse repertoire of T-cell receptors (TCR) plays a key role in the adaptive immune response to infections. Previous studies show that secondary responses to the yellow fever vaccine -the model for acute infection in humans -are weaker than primary ones, but only quantitative measurements can describe the concentration changes and lineage fates for distinct T-cell clones in vivo over time.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 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 alphabeta pairings from clonal trajectories.

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Dynamic changes in circulating T follicular helper cell composition predict neutralising antibody responses after yellow fever vaccination

et al. 2020

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Objectives. T follicular helper (Tfh) cells are the principal T helper cell subset that provides help to B cells for potent antibody responses against various pathogens. In this study, we took advantage of the live-attenuated yellow fever virus (YFV) vaccine strain, YF-17D, as a model system for studying human antiviral immune responses in vivo following exposure to an acute primary virus challenge under safe and highly controlled conditions, to comprehensively analyse the dynamics of circulating Tfh (cTfh) cells. Methods. We tracked and analysed the response of cTfh and other T and B cell subsets in peripheral blood of healthy volunteers by flow cytometry over the course of 4 weeks after YF-17D vaccination. Results. Using surface staining of cell activation markers to track YFV-specific T cells, we found increasing cTfh cell frequencies starting at day 3 and peaking around 2 weeks after YF-17D vaccination. This kinetic was confirmed in a subgroup of donors using MHC multimer staining for four known MHC class II epitopes of YF-17D. The subset composition of cTfh cells changed dynamically during the course of the immune response and was dominated by the cTfh1-polarised subpopulation. Importantly, frequencies of cTfh1 cells correlated with the strength of the neutralising antibody response, whereas frequencies of cTfh17 cells were inversely correlated. Conclusion. In summary, we describe detailed cTfh kinetics during YF-17D vaccination. Our results suggest that cTfh expansion and polarisation can serve as a ª prognostic marker for vaccine success. These insights may be leveraged in the future to improve current vaccine design and strategies.

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Precise tracking of vaccine-responding T cell clones reveals convergent and personalized response in identical twins

Cited by 117 publications

References 45 publications

T‐cell receptor and B‐cell receptor repertoire profiling in adaptive immunity

T‐cell receptor and B‐cell receptor repertoire profiling in adaptive immunity

Comprehensive analysis of antiviral adaptive immunity formation and reactivation down to single-cell level

Dynamic changes in circulating T follicular helper cell composition predict neutralising antibody responses after yellow fever vaccination

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