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Genesis of the ?? T-cell receptor.

ABSTRACT: The T-cell (TCR) repertoire relies on the diversity of receptors composed of two chains, called ? and ?, to recognize pathogens. Using results of high throughput sequencing and computational chain-pairing experiments of human TCR repertoires, we quantitively characterize the ?? generation process. We estimate the probabilities of a rescue recombination of the ? chain on the second chromosome upon failure or success on the first chromosome. Unlike ? chains, ? 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 ? 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 TCR?? is lower than 10(-12) and estimate the generation diversity and sharing properties of the ?? TCR repertoire.

SUBMITTER: Dupic T

PROVIDER: S-EPMC6417744 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Genesis of the αβ T-cell receptor.

Dupic Thomas T Marcou Quentin Q Walczak Aleksandra M AM Mora Thierry T

PLoS computational biology 20190304 3

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 bo ...[more]

PMID: 30830899

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