Publication Date:
2008-08-15
Description:
Recognition of self-antigen-derived epitopes presented by major histocompatibility complex class II (MHC II) molecules on thymic epithelial cells (TECs) is critical for the generation of a functional and self-tolerant CD4 T-cell repertoire. Whereas haematopoietic antigen-presenting cells generate MHC-II-peptide complexes predominantly through the processing of endocytosed polypeptides, it remains unknown if and how TECs use unconventional pathways of antigen presentation. Here we address the role of macroautophagy, a process that has recently been shown to allow for endogenous MHC II loading, in T-cell repertoire selection in the mouse thymus. In contrast to most other tissues, TECs had a high constitutive level of autophagy. Genetic interference with autophagy specifically in TECs led to altered selection of certain MHC-II-restricted T-cell specificities and resulted in severe colitis and multi-organ inflammation. Our findings indicate that autophagy focuses the MHC-II-peptide repertoire of TECs on their intracellular milieu, which notably comprises a wide array of otherwise strictly 'tissue-specific' self antigens. In doing so, it contributes to T-cell selection and is essential for the generation of a self-tolerant T-cell repertoire.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nedjic, Jelena -- Aichinger, Martin -- Emmerich, Jan -- Mizushima, Noboru -- Klein, Ludger -- England -- Nature. 2008 Sep 18;455(7211):396-400. doi: 10.1038/nature07208. Epub 2008 Aug 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Research Institute of Molecular Pathology, Doktor Bohr Gasse 7, 1030 Vienna, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18701890" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
*Autophagy
;
Cell Differentiation
;
Chimera/immunology
;
Colitis/genetics/immunology/metabolism
;
Epithelial Cells/cytology/immunology
;
Epithelium/*immunology
;
Female
;
Histocompatibility Antigens/immunology
;
Immune Tolerance/*immunology
;
Mice
;
Mice, Inbred C57BL
;
Microtubule-Associated Proteins/deficiency/genetics
;
Receptors, Antigen, T-Cell/immunology
;
Stromal Cells/cytology
;
T-Lymphocytes/*cytology/*immunology
;
Thymus Gland/*cytology/*immunology/transplantation
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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