T early alpha (TEA) regulates initial TCRVAJA rearrangements and leads to TCRJA coincidence

Both TCRA alleles are rearranged in mature T lymphocytes, as a result of a lack of allelic exclusion at the TRCA locus. We show in a series of T cell clones that the two TCRJA segments are not randomly, but rather coincidentally, rearranged in a given T cell. The TCRJA coincidence relies, in part, on the presence of "T early alpha" (TEA), a cis-regulatory genetic element located upstream of the TCRJA cluster. TEA promotes specific recombinational accessibility that targets primary TCRVAJA rearrangements on the 5' side of the TCRA locus. In a model of multiple waves of TCRVAJA recombination, this cis-regulatory effect of TEA allows for the scanning of the entire TCRJA cluster, thereby increasing the TCR alpha/beta diversity potential.