Two Successive Inversional V? Rearrangements on a Single Tcrb Allele Can Contribute to the TCR? Repertoire.

ABSTRACT: Mammalian TCR? loci contain 30 V? gene segments upstream and in the same transcriptional orientation as two DJC? clusters, and a downstream V? (TRBV31) in the opposite orientation. The textbook view is upstream V?s rearrange only by deletion and TRBV31 rearranges only by inversion to create V?DJC? genes. In this study, we show in mice that upstream V?s recombine through inversion to the DJC?2 cluster on alleles carrying a preassembled Trbv31-DJC?1 gene. When this gene is in-frame, Trbv5 evades TCR?-signaled feedback inhibition and recombines by inversion to the DJC?2 cluster, creating ?? T cells that express assembled Trbv5-DJC?2 genes. On alleles with an out-of-frame Trbv31-DJC?1 gene, most upstream V?s recombine at low levels and promote ?? T cell development, albeit with preferential expansion of Trbv1-DJ?2 rearrangements. Finally, we show wild-type Tcrb alleles produce mature ?? T cells that express upstream V? peptides in surface TCRs and carry Trbv31-DJ?2 rearrangements. Our study indicates two successive inversional V?-to-DJ? rearrangements on the same allele can contribute to the TCR? repertoire.

SUBMITTER: Lee KD 

PROVIDER: S-EPMC6920540 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature