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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Vydané v:	PLoS computational biology Ročník 15; číslo 3; s. e1006874
Hlavní autori:	Dupic, Thomas, Marcou, Quentin, Walczak, Aleksandra M., Mora, Thierry
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States Public Library of Science 01.03.2019 PLOS Public Library of Science (PLoS)
Predmet:	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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Popis
Shrnutí:	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.
Bibliografia:	new_version ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 The authors have declared that no competing interests exist.
ISSN:	1553-7358 1553-734X 1553-7358
DOI:	10.1371/journal.pcbi.1006874