title: The Ubiquitin-like Modifier FAT10 Is Selectively Expressed in Medullary Thymic Epithelial Cells and Modifies T Cell Selection.
abstract: HLA-F adjacent transcript 10 (FAT10) is a cytokine-inducible ubiquitin-like modifier that is highly expressed in the thymus and directly targets FAT10-conjugated proteins for degradation by the proteasome. High expression of FAT10 in the mouse thymus could be assigned to strongly autoimmune regulator-expressing, mature medullary thymic epithelial cells, which play a pivotal role in negative selection of T cells. Also in the human thymus, FAT10 is localized in the medulla but not the cortex. TCR Vβ-segment screening revealed a changed T cell repertoire in FAT10-deficient mice. Analysis of five MHC class I- and II-restricted TCR-transgenic mice demonstrated an altered thymic negative selection in FAT10-deficient mice. Furthermore, the repertoire of peptides eluted from MHC class I molecules was influenced by FAT10 expression. Hence, we identified FAT10 as a novel modifier of thymic Ag presentation and epitope-dependent elimination of self-reactive T cells, which may explain why the fat10 gene could recently be linked to enhanced susceptibility to virus-triggered autoimmune diabetes.
authors.affiliation: Division of Immunology, Department of Biology, University of Konstanz, D-78457 Konstanz, Germany;
authors.forename: Stefanie
authors.initials: S
authors.lastname: Buerger
authors.affiliation: Division of Immunology, Department of Biology, University of Konstanz, D-78457 Konstanz, Germany;
authors.forename: Valerie L
authors.initials: VL
authors.lastname: Herrmann
authors.affiliation: Division of Immunology, Department of Biology, University of Konstanz, D-78457 Konstanz, Germany;
authors.forename: Sarah
authors.initials: S
authors.lastname: Mundt
authors.affiliation: Department of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, D-72076 Tübingen, Germany; and.
authors.forename: Nico
authors.initials: N
authors.lastname: Trautwein
authors.affiliation: Division of Immunology, Department of Biology, University of Konstanz, D-78457 Konstanz, Germany; Biotechnology Institute Thurgau at the University of Konstanz, CH-8280 Kreuzlingen, Switzerland michael.basler@uni-konstanz.de marcus.groettrup@uni-konstanz.de.
authors.forename: Marcus
authors.initials: M
authors.lastname: Groettrup
authors.affiliation: Division of Immunology, Department of Biology, University of Konstanz, D-78457 Konstanz, Germany; Biotechnology Institute Thurgau at the University of Konstanz, CH-8280 Kreuzlingen, Switzerland michael.basler@uni-konstanz.de marcus.groettrup@uni-konstanz.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Basler
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D004847:Epithelial Cells / Q000276:immunology*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*; D014452:Ubiquitins / Q000502:physiology*
chemical_list: C512253:FAT10 protein, mouse; D011948:Receptors, Antigen, T-Cell; C109184:UBD protein, human; D014452:Ubiquitins