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 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.
Kasai
Michiyuki
M
Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Musashimurayama-shi, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan. kasai@nih.go.jp
Tanida
Isei
I
Ueno
Takashi
T
Kominami
Eiki
E
Seki
Sachiko
S
Ikeda
Tohru
T
Mizuochi
Toshiaki
T
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001343:Autophagy / Q000276:immunology*; D015153:Blotting, Western; D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000276:immunology* / Q000378:metabolism; D017634:Self Tolerance / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology* / Q000378:metabolism
D000949:Histocompatibility Antigens Class II; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins