The Ubiquitin-like Modifier FAT10 Is Selectively Expressed in Medullary Thymic Epithelial Cells and Modifies T Cell Selection
| Autor: | Valerie L. Herrmann, Sarah Mundt, Marcus Groettrup, Stefanie Buerger, Nico Trautwein, Michael Basler |
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| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_specialty T-Lymphocytes Immunology Antigen presentation Receptors Antigen T-Cell Thymus Gland Biology CCR8 Mice Negative selection Antigen Internal medicine MHC class I medicine Animals Humans Immunology and Allergy Ubiquitins Antigen Presentation HEK 293 cells T-cell receptor Epithelial Cells Cell biology Mice Inbred C57BL HEK293 Cells Endocrinology T cell selection biology.protein |
| Zdroj: | The Journal of Immunology. 195:4106-4116 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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