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- W4313380627 abstract "Abstract Cellular misfolded proteins are generally not transported outside the cells and thus may not be exposed to immune cells. This suggests that immune cells may not be tolerant to the cellular misfolded proteins. However, we recently found that such misfolded proteins in the endoplasmic reticulum are rescued from protein degradation and are transported to the cell surface by aberrantly expressed MHC class II molecules without being processed to peptides. Because structures of misfolded proteins associated with MHC class II molecules are different from those of normal proteins, their antigenicities are also different. On the other hand, it has been well known that MHC class II molecules are aberrantly expressed in many autoimmune diseased tissues. In this study, we extensively analyzed misfolded proteins transported to the cell surface by MHC class II molecules in autoimmune diseases and found that these misfolded proteins complexed with MHC class II molecules are specific targets for autoantibodies produced in autoimmune diseases such as rheumatoid arthritis and antiphospholipid syndrome. Furthermore, a strong correlation has been observed between autoantibody binding to misfolded protein/HLA-DR complex and the autoimmune disease susceptibility conferred by each HLA-DR allele, suggesting that misfolded protein/HLA-DR complexes are involved in the pathogenicity of autoimmune diseases. These findings imply that misfolded proteins rescued from protein degradation by aberrantly expressed MHC class II molecules function as a ‘neo-self’ antigens that might induce abnormal immune response in autoimmune diseases." @default.
- W4313380627 created "2023-01-06" @default.
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- W4313380627 date "2017-05-01" @default.
- W4313380627 modified "2023-10-12" @default.
- W4313380627 title "Cellular misfolded proteins transported to the cell surface by aberrantly expressed MHC class II molecules are major autoantibody targets in autoimmune diseases" @default.
- W4313380627 doi "https://doi.org/10.4049/jimmunol.198.supp.156.20" @default.
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