title: Generation of Novel Traj18-Deficient Mice Lacking Vα14 Natural Killer T Cells with an Undisturbed T Cell Receptor α-Chain Repertoire.
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.
authors.affiliation: Laboratory for Immune Regulation, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Kanagawa, 230-0045, Japan.|Core Research Laboratory, Mongolian National University of Medical Sciences (MNUMS), Ulaanbaatar, 14210, Mongolia.
authors.forename: Nyambayar
authors.initials: N
authors.lastname: Dashtsoodol
authors.affiliation: Laboratory for Immune Regulation, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Kanagawa, 230-0045, Japan.
authors.forename: Tomokuni
authors.initials: T
authors.lastname: Shigeura
authors.affiliation: Laboratory for Immune Regulation, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Kanagawa, 230-0045, Japan.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Ozawa
authors.affiliation: Laboratory for Immune Regulation, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Kanagawa, 230-0045, Japan.
authors.forename: Michishige
authors.initials: M
authors.lastname: Harada
authors.affiliation: Laboratory for Immune Regulation, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Kanagawa, 230-0045, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kojo
authors.affiliation: Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Kanagawa, 230-0045, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Kanagawa, 230-0045, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Koseki
authors.affiliation: Department of Human Genome Research, Kazusa DNA Research Institute, Kisarazu, Chiba, 292-0818, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Nakayama
authors.affiliation: Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Kanagawa, 230-0045, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ohara
authors.affiliation: Laboratory for Immune Regulation, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Kanagawa, 230-0045, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Taniguchi
mesh_terms: D000818:Animals; D005434:Flow Cytometry; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor / Q000235:genetics / Q000276:immunology*; D019673:Genes, T-Cell Receptor alpha / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008113:Liver Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000556:secondary; D008546:Melanoma, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology