The major histocompatibility complex: new insights from old molecules into the pathogenesis of autoimmunity

Abstract The major histocompatibility complex (MHC) is a central molecule in the immune system. The MHC is also a highly polymorphic gene that is the most strongly involved in susceptibility to many autoimmune diseases. Therefore, the elucidation of the mechanism by which specific MHC alleles are in...

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Veröffentlicht in:International immunology 2021-12, Vol.33 (12), p.641-645
1. Verfasser: Arase, Hisashi
Format: Artikel
Sprache:eng
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Zusammenfassung:Abstract The major histocompatibility complex (MHC) is a central molecule in the immune system. The MHC is also a highly polymorphic gene that is the most strongly involved in susceptibility to many autoimmune diseases. Therefore, the elucidation of the mechanism by which specific MHC alleles are involved in autoimmune disease susceptibility is important to our understanding of the pathogenesis of autoimmune diseases. Specific autoantibody production is observed in many autoimmune diseases, but the mechanism underlying their production remains unclear. We have found that MHC class II molecules exhibit a chaperone-like function to transport misfolded proteins in the endoplasmic reticulum to the outside of cells. Furthermore, misfolded proteins transported to the cell surface by MHC class II molecules of autoimmune disease risk alleles are major autoantibody targets. In this article, I propose a novel mechanism underlying autoimmune diseases mediated by misfolded proteins complexed with MHC class II molecules.
ISSN:1460-2377
1460-2377
DOI:10.1093/intimm/dxab079