Trav15-dv6 family Tcrd rearrangements diversify the Tcra repertoire

Dauphars et al. show that prior Tcrd rearrangement is essential for a combinatorially diverse Tcra repertoire in mouse thymocytes. Trav15-dv6 family Tcrd rearrangements are critical for Tcra repertoire formation because of their central and distal locations in the V-alpha-V-delta array. The Tcra repertoire is generated by multiple rounds of V-alpha-J(alpha) rearrangement. However, Tcrd recombination precedes Tcra recombination within the complex Tcra-Tcrd locus. Here, by ablating Tcrd recombination, we report that Tcrd rearrangement broadens primary V-alpha use to diversify the Tcra repertoire in mice. We reveal that use of Trav15-dv6 family V gene segments in Tcrd recombination imparts diversity in the Tcra repertoire by instigating use of central and distal V-alpha segments. Moreover, disruption of the regions containing these genes and their cis-regulatory elements identifies the Trav15-dv6 family as being responsible for driving central and distal V-alpha recombinations beyond their roles as substrates for Tcrd recombination. Our study demonstrates an indispensable role for Tcrd recombination in general, and the Trav15-dv6 family in particular, in the generation of a combinatorially diverse Tcra repertoire.

Automated summary

The study demonstrates that prior Tcrd rearrangement is essential for a diverse Tcra repertoire in mouse thymocytes. The utilization of Trav15-dv6 family V gene segments in Tcrd rearrangements imparts diversity in the Tcra repertoire through instigating the use of central and distal V-alpha segments. The study reveals the indispensable role of Tcrd recombination, particularly the Trav15-dv6 family, in generating a combinatorially diverse Tcra repertoire.