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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Bibliographic Details
Published in:	eLife Vol. 9
Main Authors:	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
Format:	Journal Article
Language:	English
Published:	England eLife Science Publications, Ltd 21.02.2020 eLife Sciences Publications Ltd eLife Sciences Publication eLife Sciences Publications, Ltd
Subjects:	Adaptive immunity Adult Analysis Antigenic determinants Antiviral agents Antiviral drugs Cloning Computational and Systems Biology Epitopes Epitopes - immunology Genetic aspects Genotype & phenotype Health aspects High-Throughput Nucleotide Sequencing Humans Immune response Immunization Immunologic Memory Immunology and Inflammation Infection Infections Life Sciences Lymphocyte Subsets - immunology Lymphocyte Subsets - physiology Lymphocytes T Male Pathogens Phenotype Phenotypes Physics Proteins Receptors, Antigen, T-Cell - genetics Receptors, Antigen, T-Cell - immunology Receptors, Antigen, T-Cell - physiology RNA sequencing single-cell Software T cell receptors T cells T-Lymphocytes - immunology T-Lymphocytes - physiology T-Lymphocytes - virology TCR Time Factors Transcriptome vaccination Vaccines Viral infections Yellow fever Yellow Fever - immunology Yellow Fever Vaccine - immunology Yellow Fever Vaccine - pharmacology Yellow fever virus - immunology computational biology systems biology TCR yellow fever inflammation single-cell human immunology vaccination
ISSN:	2050-084X, 2050-084X
Online Access:	Get full text
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 These authors contributed equally to this work.
ISSN:	2050-084X 2050-084X
DOI:	10.7554/eLife.53704