E protein binding at the Tcra enhancer promotes Tcra repertoire diversity

V(D)J recombination of antigen receptor loci is a highly developmentally regulated process. During T lymphocyte development, recombination of the Tcra gene occurs in CD4(+)CD8(+) double positive (DP) thymocytes and requires the Tcra enhancer (E & alpha;). E proteins are known regulators of DP thymocyte development and have three identified binding sites in E & alpha;. To understand the contribution of E proteins to E & alpha; function, mutants lacking one or two of the respective binding sites were generated. The double-binding site mutant displayed a partial block at the positive selection stage of & alpha;& beta; T cell development. Further investigation revealed loss of germline transcription within the Tcra locus at the J & alpha; array, along with dysregulated primary and impaired secondary V & alpha;-J & alpha; rearrangement. E & alpha; E protein binding increases Tcra locus accessibility and regulates TCR & alpha; recombination, thus directly promoting Tcra repertoire diversity.

Automated summary

The V(D)J recombination of antigen receptor loci is a highly regulated process in lymphocyte development. The recombination of Tcra gene occurs in CD4(+)CD8(+) double positive thymocytes and requires the Tcra enhancer (E & alpha;). E proteins, known regulators of DP thymocyte development, have three binding sites in E & alpha;. Mutants lacking one or two of the binding sites showed partial blockage at the positive selection stage of & alpha;& beta; T cell development, loss of germline transcription, and dysregulated gene rearrangement. The binding of E proteins to E & alpha; promotes Tcra repertoire diversity.