Defect in Rearrangement of the Most 5′ TCR–Jα Following Targeted Deletion of T Early α (TEA): Implications for TCR α Locus Accessibility

To address the role of the TEA germline transcription, which initiates upstream of the TCR–Jαs, in the regulation of TCR–Jα locus accessibility, we created a mouse in which this region has been removed by homologous recombination. Normal development of Tαβ cells and the expression of other TCR α germline transcripts in TEA −/− mice ruled out an exclusive role for TEA in the overall accessibility of the Jα cluster. However, the rearrangement of the most 5′ Jα (Jα61 to Jα53) was severely impaired, indicating that TEA may control the DNA accessibility of a particular Jα window. Moreover, the relative usage of every Jα segment was affected. These results are consistent with TEA acting as a “rearrangement-focusing” element, targeting the primary waves of Vα–Jα recombination to the most 5′ Jαs in an ongoing TCR–Jα rearrangement model.