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Genesis of the alpha beta T-cell receptor

Abstract

The T-cell (TCR) repertoire relies on the diversity of receptors composed of two chains, called α\alpha and β\beta, to recognize pathogens. Using results of high throughput sequencing and computational chain-pairing experiments of human TCR repertoires, we quantitively characterize the αβ\alpha\beta generation process. We estimate the probabilities of a rescue recombination of the β\beta chain on the second chromosome upon failure or success on the first chromosome. Unlike β\beta chains, α\alpha 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%\sim 28 \% of cells express both α\alpha chains. We report that clones sharing the same β\beta chain but different α\alpha 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\alpha\beta is lower than 101210^{-12} and estimate the generation diversity and sharing properties of the αβ\alpha\beta TCR repertoire

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