Generation of novel Traj18-deficient mice lacking Vα14 natural killer T cells with an undisturbed T cell receptor α-chain repertoire

Nyambayar Dashtsoodol, Tomokuni Shigeura, Ritsuko Ozawa, Michishige Harada, Satoshi Kojo, Takashi Watanabe, Haruhiko Koseki, Manabu Nakayama, Osamu Ohara, Masaru Taniguchi

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15 Citations (Scopus)

Abstract

Invariant Vα14 natural killer T (NKT) cells, characterized by the expression of a single invariant T cell receptor (TCR) α chain encoded by rearranged Trav11 (Vα14)-Traj18 (Jα18) gene segments in mice, and TRAV10 (Vα24)-TRAJ18 (Jα18) 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 Jα18-deficient mouse described by our group in 1997 harbors perturbed TCRα 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 TCRα chain repertoire by using next generation sequencing and by detecting normal generation of Vα19Jα33 expressing mucosal associated invariant T cells, whose development was abrogated in the originally described Jα18-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.

Original languageEnglish
Article numbere0153347
JournalPloS one
Volume11
Issue number4
DOIs
Publication statusPublished - Apr 2016
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Dashtsoodol, N., Shigeura, T., Ozawa, R., Harada, M., Kojo, S., Watanabe, T., Koseki, H., Nakayama, M., Ohara, O., & Taniguchi, M. (2016). Generation of novel Traj18-deficient mice lacking Vα14 natural killer T cells with an undisturbed T cell receptor α-chain repertoire. PloS one, 11(4), [e0153347]. https://doi.org/10.1371/journal.pone.0153347