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E proteins control the development of NKγδT cells through their invariant T cell receptor.

Publication ,  Journal Article
Mihai, A; Lee, S-Y; Shinton, S; Parker, MI; Contreras, AV; Zhang, B; Rhodes, M; Dunbrack, RL; Zúñiga-Pflücker, J-C; Ciofani, M; Zhuang, Y; Wiest, DL
Published in: Nat Commun
June 13, 2024

T cell receptor (TCR) signaling regulates important developmental transitions, partly through induction of the E protein antagonist, Id3. Although normal γδ T cell development depends on Id3, Id3 deficiency produces different phenotypes in distinct γδ T cell subsets. Here, we show that Id3 deficiency impairs development of the Vγ3+ subset, while markedly enhancing development of NKγδT cells expressing the invariant Vγ1Vδ6.3 TCR. These effects result from Id3 regulating both the generation of the Vγ1Vδ6.3 TCR and its capacity to support development. Indeed, the Trav15 segment, which encodes the Vδ6.3 TCR subunit, is directly bound by E proteins that control its expression. Once expressed, the Vγ1Vδ6.3 TCR specifies the innate-like NKγδT cell fate, even in progenitors beyond the normally permissive perinatal window, and this is enhanced by Id3-deficiency. These data indicate that the paradoxical behavior of NKγδT cells in Id3-deficient mice is determined by its stereotypic Vγ1Vδ6.3 TCR complex.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

June 13, 2024

Volume

15

Issue

1

Start / End Page

5078

Location

England

Related Subject Headings

  • T-Lymphocyte Subsets
  • Signal Transduction
  • Receptors, Antigen, T-Cell, gamma-delta
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Inhibitor of Differentiation Proteins
  • Cell Differentiation
  • Animals
 

Citation

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Mihai, A., Lee, S.-Y., Shinton, S., Parker, M. I., Contreras, A. V., Zhang, B., … Wiest, D. L. (2024). E proteins control the development of NKγδT cells through their invariant T cell receptor. Nat Commun, 15(1), 5078. https://doi.org/10.1038/s41467-024-49496-3
Mihai, Ariana, Sang-Yun Lee, Susan Shinton, Mitchell I. Parker, Alejandra V. Contreras, Baojun Zhang, Michele Rhodes, et al. “E proteins control the development of NKγδT cells through their invariant T cell receptor.Nat Commun 15, no. 1 (June 13, 2024): 5078. https://doi.org/10.1038/s41467-024-49496-3.
Mihai A, Lee S-Y, Shinton S, Parker MI, Contreras AV, Zhang B, et al. E proteins control the development of NKγδT cells through their invariant T cell receptor. Nat Commun. 2024 Jun 13;15(1):5078.
Mihai, Ariana, et al. “E proteins control the development of NKγδT cells through their invariant T cell receptor.Nat Commun, vol. 15, no. 1, June 2024, p. 5078. Pubmed, doi:10.1038/s41467-024-49496-3.
Mihai A, Lee S-Y, Shinton S, Parker MI, Contreras AV, Zhang B, Rhodes M, Dunbrack RL, Zúñiga-Pflücker J-C, Ciofani M, Zhuang Y, Wiest DL. E proteins control the development of NKγδT cells through their invariant T cell receptor. Nat Commun. 2024 Jun 13;15(1):5078.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

June 13, 2024

Volume

15

Issue

1

Start / End Page

5078

Location

England

Related Subject Headings

  • T-Lymphocyte Subsets
  • Signal Transduction
  • Receptors, Antigen, T-Cell, gamma-delta
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Inhibitor of Differentiation Proteins
  • Cell Differentiation
  • Animals