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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Main Authors:	Anastasia A Minervina, Mikhail V Pogorelyy, Ekaterina A Komech, Vadim K Karnaukhov, Petra Bacher, Elisa Rosati, Andre Franke, Dmitriy M Chudakov, Ilgar Z Mamedov, Yuri B Lebedev, Thierry Mora, Aleksandra M Walczak
Format:	Article
Language:	English
Published:	eLife Sciences Publications Ltd 2020-02-01
Series:	eLife
Subjects:	yellow fever TCR single-cell vaccination
Online Access:	https://elifesciences.org/articles/53704

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spelling	doaj-be440afc27fe45aeb9cbe3fd0dd9c7d12021-05-05T20:51:10ZengeLife Sciences Publications LtdeLife2050-084X2020-02-01910.7554/eLife.53704Primary and secondary anti-viral response captured by the dynamics and phenotype of individual T cell clonesAnastasia A Minervina0https://orcid.org/0000-0001-9884-6351Mikhail V Pogorelyy1https://orcid.org/0000-0003-0773-1204Ekaterina A Komech2Vadim K Karnaukhov3Petra Bacher4Elisa Rosati5https://orcid.org/0000-0002-2635-6422Andre Franke6Dmitriy M Chudakov7https://orcid.org/0000-0003-0430-790XIlgar Z Mamedov8Yuri B Lebedev9https://orcid.org/0000-0003-4554-4733Thierry Mora10https://orcid.org/0000-0002-5456-9361Aleksandra M Walczak11https://orcid.org/0000-0002-2686-5702Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian FederationShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Moscow, Russian FederationShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Moscow, Russian FederationCenter of Life Sciences, Skoltech, Moscow, Russian FederationInstitute of Immunology, Kiel University, Kiel, GermanyInstitute of Clinical Molecular Biology, Kiel University, Kiel, GermanyInstitute of Clinical Molecular Biology, Kiel University, Kiel, GermanyShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 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; Masaryk University, Central European Institute of Technology, Brno, Czech RepublicShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation; Masaryk University, Central European Institute of Technology, Brno, Czech Republic; V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russian FederationShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation; Moscow State University, Moscow, Russian FederationLaboratoire de physique de l’École normale supérieure, ENS, PSL, Sorbonne Université, Université de Paris, and CNRS, Paris, FranceLaboratoire de physique de l’École normale supérieure, ENS, PSL, Sorbonne Université, Université de Paris, and CNRS, Paris, FranceThe 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.https://elifesciences.org/articles/53704yellow feverTCRsingle-cellvaccination
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Anastasia A Minervina Mikhail V Pogorelyy Ekaterina A Komech Vadim K Karnaukhov Petra Bacher Elisa Rosati Andre Franke Dmitriy M Chudakov Ilgar Z Mamedov Yuri B Lebedev Thierry Mora Aleksandra M Walczak
spellingShingle	Anastasia A Minervina Mikhail V Pogorelyy Ekaterina A Komech Vadim K Karnaukhov Petra Bacher Elisa Rosati Andre Franke Dmitriy M Chudakov Ilgar Z Mamedov Yuri B Lebedev Thierry Mora Aleksandra M Walczak Primary and secondary anti-viral response captured by the dynamics and phenotype of individual T cell clones eLife yellow fever TCR single-cell vaccination
author_facet	Anastasia A Minervina Mikhail V Pogorelyy Ekaterina A Komech Vadim K Karnaukhov Petra Bacher Elisa Rosati Andre Franke Dmitriy M Chudakov Ilgar Z Mamedov Yuri B Lebedev Thierry Mora Aleksandra M Walczak
author_sort	Anastasia A Minervina
title	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_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_sort	primary and secondary anti-viral response captured by the dynamics and phenotype of individual t cell clones
publisher	eLife Sciences Publications Ltd
series	eLife
issn	2050-084X
publishDate	2020-02-01
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.
topic	yellow fever TCR single-cell vaccination
url	https://elifesciences.org/articles/53704
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Primary and secondary anti-viral response captured by the dynamics and phenotype of individual T cell clones

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