Abstract
Recently a new pathogenic mechanism for autoantibody production was proposed. Misfolded proteins bind to MHC class II in the endoplasmic reticulum and are processed to be presented at the cell surface. Misfolded proteins are not trimmed to peptides, but are presented as they are together with MHC class II molecules. Such misfolded protein/MHC class II complex can stimulate B cells, but not T cells, and will induce autoantibody production. One of such examples is the case of IgG heavy chain (IgGH). HLA class II can bind IgGH and presents it to the cell surface. Such IgGH/HLA class II complex can be recognized by rheumatoid factor. Surprisingly, RA susceptible HLA class II alleles can present IgGH efficiently, but RA resistant HLA class II alleles cannot. Therefore susceptibility to certain autoimmune diseases may be determined by the affinity of misfolded autoantigens to certain HLA class II alleles. Such new autoimmune mechanisms may explain the unexplained autoantibody production mechanisms.
