| First Author | Mihai A | Year | 2023 |
| Journal | Front Immunol | Volume | 14 |
| Pages | 1188738 | PubMed ID | 37483636 |
| Mgi Jnum | J:338557 | Mgi Id | MGI:7513208 |
| Doi | 10.3389/fimmu.2023.1188738 | Citation | Mihai A, et al. (2023) E protein binding at the Tcra enhancer promotes Tcra repertoire diversity. Front Immunol 14:1188738 |
| abstractText | 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 (Ealpha). E proteins are known regulators of DP thymocyte development and have three identified binding sites in Ealpha. To understand the contribution of E proteins to Ealpha 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 alphabeta T cell development. Further investigation revealed loss of germline transcription within the Tcra locus at the Jalpha array, along with dysregulated primary and impaired secondary Valpha-Jalpha rearrangement. Ealpha E protein binding increases Tcra locus accessibility and regulates TCRalpha recombination, thus directly promoting Tcra repertoire diversity. |
