The Ubiquitin-like Modifier FAT10 Is Selectively Expressed in Medullary Thymic Epithelial Cells and Modifies T Cell Selection

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.

Subject (DDC)

570 Biosciences, Biology

Cite This

ISO 690

BUERGER, Stefanie, Valerie L. HERRMANN, Sarah MUNDT, Nico TRAUTWEIN, Marcus GRÖTTRUP, Michael BASLER, 2015. The Ubiquitin-like Modifier FAT10 Is Selectively Expressed in Medullary Thymic Epithelial Cells and Modifies T Cell Selection. In: The Journal of Immunology. 195(9), pp. 4106-4116. ISSN 0022-1767. eISSN 1550-6606. Available under: doi: 10.4049/jimmunol.1500592

BibTex

@article{Buerger2015-11-01Ubiqu-32422,
  year={2015},
  doi={10.4049/jimmunol.1500592},
  title={The Ubiquitin-like Modifier FAT10 Is Selectively Expressed in Medullary Thymic Epithelial Cells and Modifies T Cell Selection},
  number={9},
  volume={195},
  issn={0022-1767},
  journal={The Journal of Immunology},
  pages={4106--4116},
  author={Buerger, Stefanie and Herrmann, Valerie L. and Mundt, Sarah and Trautwein, Nico and Gröttrup, Marcus and Basler, Michael}
}

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Bibliography of Konstanz

Yes