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 and , to recognize pathogens. Using results of high throughput sequencing and computational chain-pairing experiments of human TCR repertoires, we quantitively characterize the generation process. We estimate the probabilities of a rescue recombination of the chain on the second chromosome upon failure or success on the first chromosome. Unlike 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. We report that clones sharing the same chain but different 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 is lower than 10^-12 and estimate the generation diversity and sharing properties of the TCR repertoire.

Tasks

Reproductions