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

Invariant V alpha 14 natural killer T (NKT) cells, characterized by the expression of a single invariant T cell receptor (TCR) a chain encoded by rearranged Trav11 (V alpha 14)-Traj18 (J alpha 18) gene segments in mice, and TRAV10 (V alpha 24)-TRAJ18 (J alpha 18) 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 J alpha 18-deficient mouse described by our group in 1997 harbors perturbed TCRa 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 TCR alpha chain repertoire by using next generation sequencing and by detecting normal generation of V alpha 19J alpha 33 expressing mucosal associated invariant T cells, whose development was abrogated in the originally described J alpha 18-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.