Cathepsin S is not crucial to TSHR processing and presentation in a murine model of Graves' disease

• DOI: 10.1111/j.1365-2567.2005.02255.x
• Publication Date: 2005-10-25T09:04:28Z
• Authors: Mrinalini Kala; Chun‐Rong Chen; Sandra M. McLachlan; Basil Rapoport; Holly Aliesky; Harold A. Chapman
• Keywords: Thyrotropin receptor; Antigen processing

Summary 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 null mice are resistant to I‐Ab ‐ restricted experimental myasthenia gravis due inadequate presentation. To explore of Graves' disease model, I‐Ad‐restricted wild‐type (WT) –/– were immunized with adenovirus encoding A subunit thyroid stimulating hormone receptor (TSHR). TSHR develop Th1 T cells, antibodies, proportion become overtly hyperthyroid. Although presentation vitro was initially impaired mice, subsequent development similar both groups but higher antibody responses mice. WT recognized cell epitopes from panel overlapping peptides. found be I‐Ad B cells had marked defects Ii processing. These data imply that loading peptides critical becomes Ii‐independent. Contrasting findings among organ‐specific murine models uses inhibitors ameliorate autoimmunity must determined empirically.