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

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 resp...

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Autores principales: Minervina, Anastasia A, Pogorelyy, Mikhail V, Komech, Ekaterina A, Karnaukhov, Vadim K, Bacher, Petra, Rosati, Elisa, Franke, Andre, Chudakov, Dmitriy M, Mamedov, Ilgar Z, Lebedev, Yuri B, Mora, Thierry, Walczak, Aleksandra M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060039/
https://www.ncbi.nlm.nih.gov/pubmed/32081129
http://dx.doi.org/10.7554/eLife.53704
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author Minervina, Anastasia A
Pogorelyy, Mikhail V
Komech, Ekaterina A
Karnaukhov, Vadim K
Bacher, Petra
Rosati, Elisa
Franke, Andre
Chudakov, Dmitriy M
Mamedov, Ilgar Z
Lebedev, Yuri B
Mora, Thierry
Walczak, Aleksandra M
author_facet Minervina, Anastasia A
Pogorelyy, Mikhail V
Komech, Ekaterina A
Karnaukhov, Vadim K
Bacher, Petra
Rosati, Elisa
Franke, Andre
Chudakov, Dmitriy M
Mamedov, Ilgar Z
Lebedev, Yuri B
Mora, Thierry
Walczak, Aleksandra M
author_sort Minervina, Anastasia A
collection PubMed
description 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.
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spelling pubmed-70600392020-03-09 Primary and secondary anti-viral response captured by the dynamics and phenotype of individual T cell clones Minervina, Anastasia A Pogorelyy, Mikhail V Komech, Ekaterina A Karnaukhov, Vadim K Bacher, Petra Rosati, Elisa Franke, Andre Chudakov, Dmitriy M Mamedov, Ilgar Z Lebedev, Yuri B Mora, Thierry Walczak, Aleksandra M eLife Computational and Systems Biology 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. eLife Sciences Publications, Ltd 2020-02-21 /pmc/articles/PMC7060039/ /pubmed/32081129 http://dx.doi.org/10.7554/eLife.53704 Text en © 2020, Minervina et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Computational and Systems Biology
Minervina, Anastasia A
Pogorelyy, Mikhail V
Komech, Ekaterina A
Karnaukhov, Vadim K
Bacher, Petra
Rosati, Elisa
Franke, Andre
Chudakov, Dmitriy M
Mamedov, Ilgar Z
Lebedev, Yuri B
Mora, Thierry
Walczak, Aleksandra M
Primary and secondary anti-viral response captured by the dynamics and phenotype of individual T cell clones
title Primary and secondary anti-viral response captured by the dynamics and phenotype of individual T cell clones
title_full Primary and secondary anti-viral response captured by the dynamics and phenotype of individual T cell clones
title_fullStr Primary and secondary anti-viral response captured by the dynamics and phenotype of individual T cell clones
title_full_unstemmed Primary and secondary anti-viral response captured by the dynamics and phenotype of individual T cell clones
title_short Primary and secondary anti-viral response captured by the dynamics and phenotype of individual T cell clones
title_sort primary and secondary anti-viral response captured by the dynamics and phenotype of individual t cell clones
topic Computational and Systems Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060039/
https://www.ncbi.nlm.nih.gov/pubmed/32081129
http://dx.doi.org/10.7554/eLife.53704
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