Genesis of the αβ T-cell receptor

Abstract

The T-cell (TCR) repertoire relies on the diversity of receptors composed of two chains, called and {beta}, to recognize pathogens. Using results of high throughput sequencing and computational chain-pairing experiments of human TCR repertoires, we quantitively characterize the {beta} generation process. We estimate the probabilities of a rescue recombination of the {beta} chain on the second chromosome upon failure or success on the first chromosome. Unlike {beta} 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[~] 28% 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{beta} is lower than 10-12 and estimate the generation diversity and sharing properties of the {beta} TCR repertoire.