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 $\alpha$ 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 $\sim 28\%$ of cells express both $\alpha$ chains. We report that clones sharing the same $\beta$ chain but different $\alpha$ 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 TCR$\alpha \beta$ is lower than $10^{-12}$ and estimate the generation diversity and sharing properties of the $\alpha \beta$ TCR repertoire.

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Cited by in corpus (6)

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• How many different clonotypes do immune repertoires contain?
• T cell receptor binding prediction: A machine learning revolution
• Limits on Inferring T-cell Specificity from Partial Information
• Immune Fingerprinting through Repertoire Similarity