ArticleJournal of immunology (Baltimore, Md. : 1950)2015
Specification of Vδ and Vα usage by Tcra/Tcrd locus V gene segment promoters.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 16 citations in OpenAlex.
- Tnpo3 controls splicing of the pre-mRNA encoding the canonical TCR α chain of iNKT cells.Nature communications · 2023Article
- Identification of TRDV-TRAJ V domains in human and mouse T-cell receptor repertoires.Frontiers in immunology · 2023Article
- Direct regulation of TCR rearrangement and expression by E proteins during early T cell development.WIREs mechanisms of disease · 2022Review
- Trav15-dv6 family Tcrd rearrangements diversify the Tcra repertoire.The Journal of experimental medicine · 2022Article
- Abortive γδTCR rearrangements suggest ILC2s are derived from T-cell precursors.Blood advances · 2020Article
- Selected before selection: A case for inherent antigen bias in the T cell receptor repertoire.Current opinion in systems biology · 2019Article
- On the organization of human T-cell receptor loci: log-periodic distribution of T-cell receptor gene segments.Journal of the Royal Society, Interface · 2016Review
- Recent insights into the transcriptional control of the Tcra/Tcrd locus by distant enhancers during the development of T-lymphocytes.Transcription · 2015Review
- Long-Range Regulation of V(D)J Recombination.Advances in immunology · 2015Review
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
The Tcra/Tcrd locus undergoes V-Dδ-Jδ rearrangement in CD4(-)CD8(-) thymocytes to form the TCRδ chain of the γδ TCR and V-Jα rearrangement in CD4(+)CD8(+) thymocytes to form the TCRα-chain of the αβ TCR. Most V segments in the locus participate in V-Jα rearrangement, but only a small and partially overlapping subset participates in V-Dδ-Jδ rearrangement. What specifies any particular Tcra/Tcrd locus V gene segment as a Vδ, a Vα, or both is currently unknown. We tested the hypothesis that V segment usage is specified by V segment promoter-dependent chromatin accessibility in developing thymocytes. TRAV15/DV6 family V gene segments contribute to both the Tcrd and the Tcra repertoires, whereas TRAV12 family V gene segments contribute almost exclusively to the Tcra repertoire. To understand whether the TRAV15/DV6 promoter region specifies TRAV15/DV6 as a Vδ, we used gene targeting to replace the promoter region of a TRAV12 family member with one from a TRAV15/DV6 family member. The TRAV15/DV6 promoter region conferred increased germline transcription and histone modifications to TRAV12 in double-negative thymocytes and caused a substantial increase in usage of TRAV12 in Tcrd recombination events. Our results demonstrate that usage of TRAV15/DV6 family V gene segments for Tcrd recombination in double-negative thymocytes is regulated, at least in part, by intrinsic features of TRAV15/DV6 promoters, and argue that Tcra/Tcrd locus Vδ gene segments are defined by their local chromatin accessibility in CD4(-)CD8(-) thymocytes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.