DM functions differently in thymic antigen presentation cell subsets in development of autoreactive CD4+ T cells
نویسندگان
چکیده
Abstract Autoreactive CD4+ T cells broadly exist in healthy individuals and potentially cause autoimmune diseases; however, why they can escape from thymic negative selection is still controversial. We observed that the activity of DM, a peptide epitope editor MHC class II antigen presentation pathway, differentially regulated different presenting (APC). It high cTEC involved cortical positive selection, but low mTEC, B cell, pDC cDC mediate medulla, while it remains all types peripheral APC. The molecular mechanism differential regulation unknown. not directly inhibited by DO, regulator DM competes catalytic site with peptide-MHC complex, since editing those medulla APC DO−/− mice. further confirmed autoantigen MOG35–55 for vitro activation autoreactive EAE, mouse model human multiple sclerosis disease, dependent. This also true insulin B9–23 to activate restricted type 1 diabetes associated HLA-DQ8. Our findings highlighted fundamental immune system regulates thymus balance efficiency minimize autoimmunity maximum cell repertoire defend infection; DM-dependency property certain epitopes accidently caused failure deletion cells.
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ژورنال
عنوان ژورنال: Journal of Immunology
سال: 2023
ISSN: ['1550-6606', '0022-1767']
DOI: https://doi.org/10.4049/jimmunol.210.supp.170.03