title: NKT cell-TCR expression activates conventional T cells in vivo, but is largely dispensable for mature NKT cell biology.
abstract: Natural killer T (NKT) cell development depends on recognition of self-glycolipids via their semi-invariant Vα14i-TCR. However, to what extent TCR-mediated signals determine identity and function of mature NKT cells remains incompletely understood. To address this issue, we developed a mouse strain allowing conditional Vα14i-TCR expression from within the endogenous Tcrα locus. We demonstrate that naïve T cells are activated upon replacement of their endogenous TCR repertoire with Vα14i-restricted TCRs, but they do not differentiate into NKT cells. On the other hand, induced TCR ablation on mature NKT cells did not affect their lineage identity, homeostasis, or innate rapid cytokine secretion abilities. We therefore propose that peripheral NKT cells become unresponsive to and thus are independent of their autoreactive TCR.
authors.affiliation: Molecular Immunology and Signaltransduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: J Christoph
authors.initials: JC
authors.lastname: Vahl
authors.forename: Klaus
authors.initials: K
authors.lastname: Heger
authors.forename: Nathalie
authors.initials: N
authors.lastname: Knies
authors.forename: Marco Y
authors.initials: MY
authors.lastname: Hein
authors.forename: Louis
authors.initials: L
authors.lastname: Boon
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Bojan
authors.initials: B
authors.lastname: Polic
authors.forename: Marc
authors.initials: M
authors.lastname: Schmidt-Supprian
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D019070:Cell Lineage; D016207:Cytokines / Q000378:metabolism; D055879:Gene Knock-In Techniques; D006706:Homeostasis; D007113:Immunity, Innate / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D018655:Lymphocyte Count; D051379:Mice; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000166:cytology* / Q000276:immunology*; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D013997:Time Factors
chemical_list: D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta