Poor Quality Vβ Recombination Signal Sequences Enforce TCRβ Allelic Exclusion by Limiting the Frequency of Vβ Recombination

Monoallelic expression (allelic exclusion) of T and B lymphocyte antigen receptor genes is achieved by the assembly of a functional gene through V(D)J recombination on one allele and subsequent feedback inhibition of recombination on the other allele. There has been no validated mechanism for how only one allele of any antigen receptor locus assembles a functional gene prior to feedback inhibition. Here, we demonstrate that replacement of a single V{beta} recombination signal sequence (RSS) with a better RSS increases V{beta} rearrangement, reveals Tcrb alleles compete for utilization in the {beta} T cell receptor (TCR) repertoire, and elevates the fraction of {beta} T cells expressing TCR{beta} protein from both alleles. The data indicate that poor qualities of V{beta} RSSs for recombination with D{beta} and J{beta} RSSs enforces allelic exclusion by stochastically limiting the incidence of functional V{beta} rearrangements on both alleles before feedback inhibition terminates V{beta} recombination.