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ImmunologyNature Communications
Peer-reviewed journal article

E protein control of NKgammadeltaT cell development through both generation and function of the stereotypic Vgamma1Vdelta6.3 TCR

Ariana MihaiiD, Sang-Yun LeeiD, Susan A. ShintoniD, Mitchell I. ParkeriD, Alejandra Virginia ContrerasiD, Baojun ZhangiD, Michele R. RhodesiD, Roland L. DunbrackiD, Juan Carlos Zúñiga‐PflückeriD, Maria CiofaniiD, Yuan ZhuangiD, David L. WiestiD

Abstract

T cell receptor (TCR) signals regulate important developmental transitions through induction of the E protein antagonist, Id3; however, Id3-deficiency produces paradoxical effects on {gamma}{delta} T cell subsets. Here, we show here that Id3-deficiency attenuates the development of V{gamma}3-expressing {gamma}{delta} T cells, while markedly enhancing the development of V{gamma}1V{delta}6.3-expressing NK{gamma}{delta}T cells. Id3-deficiency does so by regulating both the generation of the stereotypic V{gamma}1V{delta}6.3 TCR expressed by NK{gamma}{delta}T cells and its capacity to support development. Indeed, we determined that the Trav15 segment, which encodes the V{delta}6.3 TCR subunit, is directly bound by E proteins that control its expression. Moreover, once expressed, the resulting V{gamma}1V{delta}6.3 TCR in capable of specifying the innate-like NK{gamma}{delta}T cell fate in a cell-autonomous and developmentally-unrestricted manner that is restrained by the Id3/E axis. Together, these data indicate that the paradoxical behavior of NK{gamma}{delta}T cells in the Id3-deficient setting is entirely determined by its stereotypic V{gamma}1V{delta}6.3 TCR complex.

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