[Misfolded proteins complexed with HLA class II molecules are involved in autoimmune diseases as a target for autoantibodies]

Abstract

HLA class II molecules play an important role in immune response by presenting peptide antigens to T cells. However, when misfolded proteins in endoplasmic reticulum, which are generally degraded in the cells, are associated with MHC class II molecules instead of invariant chain, the misfolded proteins are transported to the cell surface without processing to peptides. Furthermore, misfolded proteins associated with MHC class II molecules are recognized by autoantibodies produced in autoimmune diseases such as rheumatoid arthritis and antiphospholipid syndrome. More importantly, autoantibody binding to misfolded protein/MHC class II complex is associated with susceptibility to rheumatoid arthritis conferred by each MHC class II allele. Therefore, cellular misfolded proteins rescued from degradation by MHC class II molecules seem to be involved in autoimmune diseases as a target for autoantibodies.