| First Author | Lee KD | Year | 2020 |
| Journal | J Immunol | Volume | 204 |
| Issue | 1 | Pages | 78-86 |
| PubMed ID | 31740488 | Mgi Jnum | J:294816 |
| Mgi Id | MGI:6451386 | Doi | 10.4049/jimmunol.1901105 |
| Citation | Lee KD, et al. (2020) Two Successive Inversional Vbeta Rearrangements on a Single Tcrb Allele Can Contribute to the TCRbeta Repertoire. J Immunol 204(1):78-86 |
| abstractText | Mammalian TCRbeta loci contain 30 Vbeta gene segments upstream and in the same transcriptional orientation as two DJCbeta clusters, and a downstream Vbeta (TRBV31) in the opposite orientation. The textbook view is upstream Vbetas rearrange only by deletion and TRBV31 rearranges only by inversion to create VbetaDJCbeta genes. In this study, we show in mice that upstream Vbetas recombine through inversion to the DJCbeta2 cluster on alleles carrying a preassembled Trbv31-DJCbeta1 gene. When this gene is in-frame, Trbv5 evades TCRbeta-signaled feedback inhibition and recombines by inversion to the DJCbeta2 cluster, creating alphabeta T cells that express assembled Trbv5-DJCbeta2 genes. On alleles with an out-of-frame Trbv31-DJCbeta1 gene, most upstream Vbetas recombine at low levels and promote alphabeta T cell development, albeit with preferential expansion of Trbv1-DJbeta2 rearrangements. Finally, we show wild-type Tcrb alleles produce mature alphabeta T cells that express upstream Vbeta peptides in surface TCRs and carry Trbv31-DJbeta2 rearrangements. Our study indicates two successive inversional Vbeta-to-DJbeta rearrangements on the same allele can contribute to the TCRbeta repertoire. |
