Molecular generation of TRECs during thymic differentiation of T cells. DN thymocytes first undergo rearrangement of the TCRB locus (encoding segments of the TCR-β chain). This begins with the rearrangement of the TCRBD to TCRBJ, which gives rise to several DβJβTRECs, and is followed by the recombination of V to DJ segments, which generates a greater variety of VDβTRECs (A). The TCRA locus is rearranged next, which, similarly to the β-chain, is characterized by enormous diversity. However, a common requirement for productive TCRAVJ recombination is deletion of the TCRD locus that it encompasses. This 2-step process gives rise to a signal joint TREC and a coding joint TREC (B). Both DNA families of TRECs are stable and do not replicate during mitosis. These sequences are unique to naive αβ T cells. As a result, TRECs serve as a valuable marker of RTEs and their levels are indicative of thymic activity.