Generation of Novel Traj18-Deficient Mice Lacking Vα14 Natural Killer T Cells with an Undisturbed T Cell Receptor α-Chain RepertoireReport as inadecuate




Generation of Novel Traj18-Deficient Mice Lacking Vα14 Natural Killer T Cells with an Undisturbed T Cell Receptor α-Chain Repertoire - Download this document for free, or read online. Document in PDF available to download.

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.



Author: Nyambayar Dashtsoodol, Tomokuni Shigeura, Ritsuko Ozawa, Michishige Harada, Satoshi Kojo, Takashi Watanabe, Haruhiko Koseki, Mana

Source: http://plos.srce.hr/



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