A dynamical model of TCRβ gene recombination: Coupling the initiation of Dβ-Jβ rearrangement to TCRβ allelic exclusion

One paradigm of random monoallelic gene expression is that of T-cell receptor (TCR)β allelic exclusion in T lymphocytes. However, the dynamics that sustain asymmetric choice in TCRβ dual allele usage and the production of TCRβ monoallelic expressing T-cells remain poorly understood. Here, we develop a computational model to explore a scheme of TCRβ allelic exclusion based on the stochastic initiation of DNA rearrangement [V(D)J recombination] at homologous alleles in T-cell progenitors, and thus account for the genotypic profiles typically associated with allelic exclusion in differentiated T-cells. Disturbances in these dynamics at the level of an individual allele have limited consequences on these profiles, a robust feature of the system that is underscored by our simulations. Our study predicts a biological system in which locus-specific, prime epigenetic allelic activation effects set the stage to both optimize the production of TCRβ allelically excluded T-cells and curtail the emergence of their allelically included counterparts.