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Publication : Generation of Novel Traj18-Deficient Mice Lacking Vα14 Natural Killer T Cells with an Undisturbed T Cell Receptor α-Chain Repertoire.

First Author  Dashtsoodol N Year  2016
Journal  PLoS One Volume  11
Issue  4 Pages  e0153347
PubMed ID  27064277 Mgi Jnum  J:249268
Mgi Id  MGI:6093062 Doi  10.1371/journal.pone.0153347
Citation  Dashtsoodol N, et al. (2016) Generation of Novel Traj18-Deficient Mice Lacking Valpha14 Natural Killer T Cells with an Undisturbed T Cell Receptor alpha-Chain Repertoire. PLoS One 11(4):e0153347
abstractText  Invariant Valpha14 natural killer T (NKT) cells, characterized by the expression of a single invariant T cell receptor (TCR) alpha chain encoded by rearranged Trav11 (Valpha14)-Traj18 (Jalpha18) gene segments in mice, and TRAV10 (Valpha24)-TRAJ18 (Jalpha18) in humans, mediate adjuvant effects to activate various effector cell types in both innate and adaptive immune systems that facilitates the potent antitumor effects. It was recently reported that the Jalpha18-deficient mouse described by our group in 1997 harbors perturbed TCRalpha repertoire, which raised concerns regarding the validity of some of the experimental conclusions that have been made using this mouse line. To resolve this concern, we generated a novel Traj18-deficient mouse line by specifically targeting the Traj18 gene segment using Cre-Lox approach. Here we showed the newly generated Traj18-deficient mouse has, apart from the absence of Traj18, an undisturbed TCRalpha chain repertoire by using next generation sequencing and by detecting normal generation of Valpha19Jalpha33 expressing mucosal associated invariant T cells, whose development was abrogated in the originally described Jalpha18-KO mice. We also demonstrated here the definitive requirement for NKT cells in the protection against tumors and their potent adjuvant effects on antigen-specific CD8 T cells.
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