Genesis of the alpha beta T-cell receptor
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 $\sim 28 \%$ 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 TCR$αβ$ is lower than $10^{-12}$ and estimate the generation diversity and sharing properties of the $αβ$ TCR repertoire.