Abstract |
By regulating invariant (Ii) chain processing and MHC class II peptide loading, the endosomal protease cathepsin S (Cat S) has a potential role in autoimmune susceptibility. Indeed, Cat S null mice are resistant to I-Ab-restricted experimental myasthenia gravis due to inadequate peptide presentation. To explore the role of Cat S in a Graves' disease model, I-Ad-restricted wild-type (WT) and Cat S(-/-) mice were immunized with adenovirus encoding the A subunit of thyroid stimulating hormone receptor (TSHR). TSHR adenovirus immunized mice develop Th1 T cells, TSHR antibodies, and a proportion become overtly hyperthyroid. Although TSHR presentation in vitro was initially impaired in Cat S(-/-) mice, subsequent TSHR presentation in vitro and disease development were similar in both groups but with higher antibody responses in Cat S null mice. WT and Cat S(-/-) mice recognized similar T cell epitopes from a panel of overlapping TSHR peptides. TSHR responses were found to be I-Ad-restricted and Cat S(-/-) I-Ad B cells had marked defects in Ii processing. These data imply that loading of TSHR peptides critical to TSHR antibody responses becomes Ii-independent. Contrasting findings among organ-specific murine autoimmune models imply that potential uses of Cat S inhibitors to ameliorate autoimmunity must be determined empirically.
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Authors | Mrinalini Kala, Chun-Rong Chen, Sandra M McLachlan, Basil Rapoport, Holly Aliesky, Harold A Chapman |
Journal | Immunology
(Immunology)
Vol. 116
Issue 4
Pg. 532-40
(Dec 2005)
ISSN: 0019-2805 [Print] England |
PMID | 16313367
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens, Differentiation, B-Lymphocyte
- Autoantibodies
- Epitopes, T-Lymphocyte
- Histocompatibility Antigens Class II
- Receptors, Thyrotropin
- invariant chain
- Cathepsins
- cathepsin S
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Topics |
- Adenoviridae
(genetics)
- Animals
- Antigen Presentation
(immunology)
- Antigens, Differentiation, B-Lymphocyte
(immunology)
- Autoantibodies
(biosynthesis)
- Cathepsins
(immunology)
- Disease Models, Animal
- Epitopes, T-Lymphocyte
(immunology)
- Female
- Genetic Vectors
- Graves Disease
(immunology, physiopathology)
- Histocompatibility Antigens Class II
(immunology)
- Immunization
- Mice
- Mice, Inbred BALB C
- Receptors, Thyrotropin
(genetics, immunology)
- Th1 Cells
(immunology)
- Thyroid Gland
(physiopathology)
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