Autophagic Compartments Gain Access to the MHC Class II Compartments in Thymic Epithelium

The presentation of self-peptides in the context of MHC molecules by thymic epithelial cells (TECs) is essential for T cell repertoire selection in the thymus. However, the underlying mechanisms of this process have not been fully elucidated. To address whether autophagy, a catabolic process involvi...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2009-12, Vol.183 (11), p.7278-7285
Main Authors: Kasai, Michiyuki, Tanida, Isei, Ueno, Takashi, Kominami, Eiki, Seki, Sachiko, Ikeda, Tohru, Mizuochi, Toshiaki
Format: Article
Language:English
Subjects:
Animals
Antigen Presentation - immunology
Autophagy - immunology
Blotting, Western
Cell Line
Epithelial Cells - immunology
Epithelial Cells - metabolism
Histocompatibility Antigens Class II - immunology
Histocompatibility Antigens Class II - metabolism
Mice
Mice, Inbred C57BL
Microscopy, Fluorescence
Microtubule-Associated Proteins - immunology
Microtubule-Associated Proteins - metabolism
Self Tolerance - immunology
Thymus Gland - immunology
Thymus Gland - metabolism
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Summary:The presentation of self-peptides in the context of MHC molecules by thymic epithelial cells (TECs) is essential for T cell repertoire selection in the thymus. However, the underlying mechanisms of this process have not been fully elucidated. To address whether autophagy, a catabolic process involving the degradation of a cell's components through the lysosomal machinery, intersects the MHC class II-restricted Ag presentation pathway in TECs, we investigated the colocalization of LC3, a peculiar autophagy marker molecule, with MHC class II compartments in in vitro-established TEC lines by immunofluorescence microscopy and Western blotting analyses. We found that in both cortical and medullary TEC lines, LC3 was colocalized with the H2-DM-positive lysosomal compartments, in which MHC class II plus class II-associated invariant chain peptides complexes are formed. Furthermore, our analysis of thymic cryosections from 1-day-old mice revealed that LC3 colocalizes with the H2-DM-positive compartments in TECs. These results strongly suggest that the cytoplasmic self-Ags gain access to the H2-DM-positive compartments via the autophagic process in the thymus.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.0804087