Genesis of the αβ T-cell receptor

Abstract : 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 *35% of cells express both α 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 TCRαβ is lower than 10 −12 and estimate the generation diversity and sharing properties of the αβ TCR repertoire. Author summary Receptors on the surface of T-cells recognize pathogens and initiate an immune response. Analyzing the sequences of human T-cell receptors we draw a detailed quantitative picture of the generation process of the two receptor chains allowing us to estimate the diversity of the complete repertoire. We discuss which elements of the receptor production processes are correlated and which are independent, proposing mechanistic models at the origin of the correlations. We discuss the implications of our findings for the functional role of each of these cells, and the diversity of the repertoire.
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Submitted on : Monday, May 6, 2019 - 12:30:09 PM
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Thomas Dupic, Quentin Marcou, Aleksandra Walczak, Thierry Mora. Genesis of the αβ T-cell receptor. PLoS Computational Biology, Public Library of Science, 2019, 15 (3), pp.e1006874. ⟨10.1371/journal.pcbi.1006874⟩. ⟨hal-02120964⟩



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