A discrete chromatin loop in the mouse Tcra-Tcrd locus shapes the TCRδ and TCRα repertoires

The locus encoding the T cell antigen receptor (TCR) alpha-chain and delta-chain (Tcra-Tcrd) undergoes recombination of its variable-diversity-joining (V(D)J) segments in CD4(-)CD8(-) double-negative thymocytes and CD4(+)CD8(+) double-positive thymocytes to generate diverse TCR delta repertoires and TCR alpha repertoires, respectively. Here we identified a chromatin-interaction network in the Tcra-Tcrd locus in double-negative thymocytes that was formed by interactions between binding elements for the transcription factor CTCF. Disruption of a discrete chromatin loop encompassing the D, J and constant (C) segments of Tcrd allowed a single V segment to frequently contact and rearrange to D and J segments and dominate the adult TCR delta repertoire. Disruption of this loop also narrowed the TCR alpha repertoire, which, we believe, followed as a consequence of the restricted TCR delta repertoire. Hence, a single CTCF-mediated chromatin loop directly regulated TCR delta diversity and indirectly regulated TCR alpha diversity.