Inefficient V(D)J recombination underlies monogenic T cell receptor β expression.

The assembly of T cell receptor (TCR) and immunoglobulin (Ig) genes by V(D)J recombination generates the antigen receptor (AgR) diversity that is vital for adaptive immunity. At most AgR loci, V(D)J recombination is regulated so that only one allele assembles a functional gene, ensuring that nearly every T and B cell expresses a single type, or specificity, of AgR. The genomic organizations of some AgR loci permit the assembly and expression of two distinct genes on each allele; however, this is prevented by undetermined mechanisms. We show that the poor qualities of recombination signal sequences (RSSs) flanking Vβ gene segments suppress the assembly and expression of two distinct TCRβ genes from a single allele. Our data demonstrate that an intrinsic genetic mechanism that stochastically limits Vβ recombination efficiency governs monogenic TCRβ expression, thereby restraining the expression of multiple AgRs on αβ T cells.