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Genesis of the αβ T-cell receptor

By Thomas Dupic, Quentin Marcou, Aleksandra M Walczak, Thierry Mora

Posted 28 Jun 2018
bioRxiv DOI: 10.1101/353128 (published DOI: 10.1371/journal.pcbi.1006874)

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 ~ 28% of cells express both α chains. We report that clones sharing the same β chain but different α chains are overrepresented, suggesting that they respond to common immune challenges. 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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