Genesis of the $αβ$ T-cell Receptor. Dupic, T., Marcou, Q., Walczak, A. M., & Mora, T. PLOS Computational Biology, 15(3):e1006874, March, 2019. doi abstract bibtex 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 TCR$αβ$ is lower than 10-12 and estimate the generation diversity and sharing properties of the $αβ$ TCR repertoire.
@article{dupicGenesisAvTcell2019,
title = {Genesis of the {$\alpha\beta$} {{T-cell}} Receptor},
author = {Dupic, Thomas and Marcou, Quentin and Walczak, Aleksandra M. and Mora, Thierry},
year = {2019},
month = mar,
journal = {PLOS Computational Biology},
volume = {15},
number = {3},
pages = {e1006874},
issn = {1553-7358},
doi = {10.1371/journal.pcbi.1006874},
urldate = {2019-08-08},
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 {$\sim$}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 10-12 and estimate the generation diversity and sharing properties of the {$\alpha\beta$} TCR repertoire.},
langid = {english},
keywords = {Chromosome structure and function,Chromosomes,Cloning,DNA sequence analysis,Nucleotide sequencing,Sequence analysis,T cell receptors,T cells},
file = {/home/thomas/snap/zotero-snap/common/Zotero/storage/KIME36YP/Dupic et al. - 2019 - Genesis of the αβ T-cell receptor.pdf;/home/thomas/snap/zotero-snap/common/Zotero/storage/B2SX53MF/article.html}
}
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