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Tcrd Rearrangement Redirects a Processive Tcra Recombination Program to Expand the Tcra Repertoire.

Publication ,  Journal Article
Carico, ZM; Roy Choudhury, K; Zhang, B; Zhuang, Y; Krangel, MS
Published in: Cell Rep
June 6, 2017

Adaptive immunity depends on diverse T cell receptor repertoires generated by variable, diversity, and joining (V[D]J) recombination. Here, we define the principles by which combinatorial diversity is generated in the murine Tcra repertoire. Tcra and Tcrd gene segments share the Tcra-Tcrd locus, with interspersed Vα and Vδ segments undergoing Vδ-Dδ-Jδ rearrangement in CD4-CD8- thymocytes and then multiple rounds of Vα-Jα rearrangement in CD4+CD8+ thymocytes. We document stepwise, highly coordinated proximal-to-distal progressions of Vα and Jα use on individual Tcra alleles, limiting combinatorial diversity. This behavior is supported by an extended chromatin conformation in CD4+CD8+ thymocytes, with only nearby Vα and Jα segments contacting each other. Tcrd rearrangements can use distal Vδ segments due to a contracted Tcra-Tcrd conformation in CD4-CD8- thymocytes. These rearrangements expand the Tcra repertoire by truncating the Vα array to permit otherwise disfavored Vα-Jα combinations. Therefore, recombination events at two developmental stages with distinct chromatin conformations synergize to promote Tcra repertoire diversity.

Duke Scholars

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Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

June 6, 2017

Volume

19

Issue

10

Start / End Page

2157 / 2173

Location

United States

Related Subject Headings

  • V(D)J Recombination
  • Thymocytes
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Antigen, T-Cell, alpha-beta
  • Models, Genetic
  • Mice, Knockout
  • Mice
  • Animals
  • 31 Biological sciences
  • 1116 Medical Physiology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Carico, Z. M., Roy Choudhury, K., Zhang, B., Zhuang, Y., & Krangel, M. S. (2017). Tcrd Rearrangement Redirects a Processive Tcra Recombination Program to Expand the Tcra Repertoire. Cell Rep, 19(10), 2157–2173. https://doi.org/10.1016/j.celrep.2017.05.045
Carico, Zachary M., Kingshuk Roy Choudhury, Baojun Zhang, Yuan Zhuang, and Michael S. Krangel. “Tcrd Rearrangement Redirects a Processive Tcra Recombination Program to Expand the Tcra Repertoire.Cell Rep 19, no. 10 (June 6, 2017): 2157–73. https://doi.org/10.1016/j.celrep.2017.05.045.
Carico ZM, Roy Choudhury K, Zhang B, Zhuang Y, Krangel MS. Tcrd Rearrangement Redirects a Processive Tcra Recombination Program to Expand the Tcra Repertoire. Cell Rep. 2017 Jun 6;19(10):2157–73.
Carico, Zachary M., et al. “Tcrd Rearrangement Redirects a Processive Tcra Recombination Program to Expand the Tcra Repertoire.Cell Rep, vol. 19, no. 10, June 2017, pp. 2157–73. Pubmed, doi:10.1016/j.celrep.2017.05.045.
Carico ZM, Roy Choudhury K, Zhang B, Zhuang Y, Krangel MS. Tcrd Rearrangement Redirects a Processive Tcra Recombination Program to Expand the Tcra Repertoire. Cell Rep. 2017 Jun 6;19(10):2157–2173.
Journal cover image

Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

June 6, 2017

Volume

19

Issue

10

Start / End Page

2157 / 2173

Location

United States

Related Subject Headings

  • V(D)J Recombination
  • Thymocytes
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Antigen, T-Cell, alpha-beta
  • Models, Genetic
  • Mice, Knockout
  • Mice
  • Animals
  • 31 Biological sciences
  • 1116 Medical Physiology