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Trav15-dv6 family Tcrd rearrangements diversify the Tcra repertoire.

Publication ,  Journal Article
Dauphars, DJ; Mihai, A; Wang, L; Zhuang, Y; Krangel, MS
Published in: J Exp Med
February 7, 2022

The Tcra repertoire is generated by multiple rounds of Vα-Jα 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 Vα 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 Vα 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 Vα 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.

Duke Scholars

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Published In

J Exp Med

DOI

EISSN

1540-9538

Publication Date

February 7, 2022

Volume

219

Issue

2

Location

United States

Related Subject Headings

  • V(D)J Recombination
  • Thymocytes
  • T-Lymphocytes
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Antigen, T-Cell, alpha-beta
  • Mice, Knockout
  • Mice
  • Immunology
  • High-Throughput Nucleotide Sequencing
  • Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor
 

Citation

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Dauphars, D. J., Mihai, A., Wang, L., Zhuang, Y., & Krangel, M. S. (2022). Trav15-dv6 family Tcrd rearrangements diversify the Tcra repertoire. J Exp Med, 219(2). https://doi.org/10.1084/jem.20211581
Dauphars, Danielle J., Ariana Mihai, Liuyang Wang, Yuan Zhuang, and Michael S. Krangel. “Trav15-dv6 family Tcrd rearrangements diversify the Tcra repertoire.J Exp Med 219, no. 2 (February 7, 2022). https://doi.org/10.1084/jem.20211581.
Dauphars DJ, Mihai A, Wang L, Zhuang Y, Krangel MS. Trav15-dv6 family Tcrd rearrangements diversify the Tcra repertoire. J Exp Med. 2022 Feb 7;219(2).
Dauphars, Danielle J., et al. “Trav15-dv6 family Tcrd rearrangements diversify the Tcra repertoire.J Exp Med, vol. 219, no. 2, Feb. 2022. Pubmed, doi:10.1084/jem.20211581.
Dauphars DJ, Mihai A, Wang L, Zhuang Y, Krangel MS. Trav15-dv6 family Tcrd rearrangements diversify the Tcra repertoire. J Exp Med. 2022 Feb 7;219(2).

Published In

J Exp Med

DOI

EISSN

1540-9538

Publication Date

February 7, 2022

Volume

219

Issue

2

Location

United States

Related Subject Headings

  • V(D)J Recombination
  • Thymocytes
  • T-Lymphocytes
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Antigen, T-Cell, alpha-beta
  • Mice, Knockout
  • Mice
  • Immunology
  • High-Throughput Nucleotide Sequencing
  • Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor