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E protein binding at the Tcra enhancer promotes Tcra repertoire diversity.

Publication ,  Journal Article
Mihai, A; Roy, S; Krangel, MS; Zhuang, Y
Published in: Front Immunol
2023

V(D)J recombination of antigen receptor loci is a highly developmentally regulated process. During T lymphocyte development, recombination of the Tcra gene occurs in CD4+CD8+ double positive (DP) thymocytes and requires the Tcra enhancer (Eα). E proteins are known regulators of DP thymocyte development and have three identified binding sites in Eα. To understand the contribution of E proteins to Eα function, mutants lacking one or two of the respective binding sites were generated. The double-binding site mutant displayed a partial block at the positive selection stage of αβ T cell development. Further investigation revealed loss of germline transcription within the Tcra locus at the Jα array, along with dysregulated primary and impaired secondary Vα-Jα rearrangement. Eα E protein binding increases Tcra locus accessibility and regulates TCRα recombination, thus directly promoting Tcra repertoire diversity.

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Published In

Front Immunol

DOI

EISSN

1664-3224

Publication Date

2023

Volume

14

Start / End Page

1188738

Location

Switzerland

Related Subject Headings

  • V(D)J Recombination
  • Transcription Factors
  • Thymocytes
  • Receptors, Antigen, T-Cell, alpha-beta
  • Protein Binding
  • Enhancer Elements, Genetic
  • 3204 Immunology
  • 3105 Genetics
  • 3101 Biochemistry and cell biology
  • 1108 Medical Microbiology
 

Citation

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Mihai, A., Roy, S., Krangel, M. S., & Zhuang, Y. (2023). E protein binding at the Tcra enhancer promotes Tcra repertoire diversity. Front Immunol, 14, 1188738. https://doi.org/10.3389/fimmu.2023.1188738
Mihai, Ariana, Sumedha Roy, Michael S. Krangel, and Yuan Zhuang. “E protein binding at the Tcra enhancer promotes Tcra repertoire diversity.Front Immunol 14 (2023): 1188738. https://doi.org/10.3389/fimmu.2023.1188738.
Mihai A, Roy S, Krangel MS, Zhuang Y. E protein binding at the Tcra enhancer promotes Tcra repertoire diversity. Front Immunol. 2023;14:1188738.
Mihai, Ariana, et al. “E protein binding at the Tcra enhancer promotes Tcra repertoire diversity.Front Immunol, vol. 14, 2023, p. 1188738. Pubmed, doi:10.3389/fimmu.2023.1188738.
Mihai A, Roy S, Krangel MS, Zhuang Y. E protein binding at the Tcra enhancer promotes Tcra repertoire diversity. Front Immunol. 2023;14:1188738.

Published In

Front Immunol

DOI

EISSN

1664-3224

Publication Date

2023

Volume

14

Start / End Page

1188738

Location

Switzerland

Related Subject Headings

  • V(D)J Recombination
  • Transcription Factors
  • Thymocytes
  • Receptors, Antigen, T-Cell, alpha-beta
  • Protein Binding
  • Enhancer Elements, Genetic
  • 3204 Immunology
  • 3105 Genetics
  • 3101 Biochemistry and cell biology
  • 1108 Medical Microbiology