Genesis of the [alpha][beta] T-cell receptor

The T-cell (TCR) repertoire relies on the diversity of receptors composed of two chains, called [alpha] and [beta], to recognize pathogens. Using results of high throughput sequencing and computational chain-pairing experiments of human TCR repertoires, we quantitively characterize the [alpha][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, [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 ~35% of cells express both [alpha] 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[alpha][beta] is lower than 10.sup.-12 and estimate the generation diversity and sharing properties of the [alpha][beta] TCR repertoire.