Genesis of the αβ T-cell receptor

The T-cell (TCR) repertoire relies on the diversity of receptors composed of two chains, called α and β, to recognize pathogens. Using results of high throughput sequencing and computational chain-pairing experiments of human TCR repertoires, we quantitively characterize the αβ generation process. W...

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Veröffentlicht in:PLoS computational biology Jg. 15; H. 3; S. e1006874
Hauptverfasser: Dupic, Thomas, Marcou, Quentin, Walczak, Aleksandra M., Mora, Thierry
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Public Library of Science 01.03.2019
PLOS
Public Library of Science (PLoS)
Schlagworte:
Biochemistry, Molecular Biology
Bioinformatics
Biology and Life Sciences
Chains
Chromosomes
Chromosomes, Human
Cloning
Computer applications
Genes
Genomics
Humans
Immune system
Immunology
Life Sciences
Lymphocytes
Lymphocytes T
Medicine and Health Sciences
Next-generation sequencing
Probability
Receptors
Receptors, Antigen, T-Cell, alpha-beta - biosynthesis
Receptors, Antigen, T-Cell, alpha-beta - genetics
Receptors, Antigen, T-Cell, alpha-beta - immunology
Recombination
Recombination, Genetic
Research and Analysis Methods
Statistical analysis
T cell receptors
T-cell receptor
France
DNA sequence analysis
Cloning
T cell receptors
Chromosome structure and function
Nucleotide sequencing
T cells
Chromosomes
Sequence analysis
ISSN:1553-7358, 1553-734X, 1553-7358
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Zusammenfassung:The T-cell (TCR) repertoire relies on the diversity of receptors composed of two chains, called α and β, to recognize pathogens. Using results of high throughput sequencing and computational chain-pairing experiments of human TCR repertoires, we quantitively characterize the αβ generation process. We estimate the probabilities of a rescue recombination of the β chain on the second chromosome upon failure or success on the first chromosome. Unlike β chains, α chains recombine simultaneously on both chromosomes, resulting in correlated statistics of the two genes which we predict using a mechanistic model. We find that ∼35% of cells express both α chains. Altogether, our statistical analysis gives a complete quantitative mechanistic picture that results in the observed correlations in the generative process. We learn that the probability to generate any TCRαβ is lower than 10(-12) and estimate the generation diversity and sharing properties of the αβ TCR repertoire.
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The authors have declared that no competing interests exist.
ISSN:1553-7358
1553-734X
1553-7358
DOI:10.1371/journal.pcbi.1006874