Molecular and pathogenic effects of endoplasmic reticulum aminopeptidases ERAP1 and ERAP2 in MHC I associated inflammatory disorders: Towards a unifying view.
The inflammatory diseases that are most strongly associated with major histocompatibility Complex class I (MHC I) alleles are also influenced by endoplasmic reticulum aminopeptidase (ERAP) 1 and/or 2, often in epistasis with the susceptibility MHC I allele. This review will focus on the four major MHC I associated inflammatory disorders: ankylosing spondylitis, birdshot chorioretinopathy, Behcet's disease and psoriasis. The genetics of ERAP1/ERAP2 association and the alterations induced by polymorphism of these enzymes on the risk MHC I allotypes will be examined. A pattern emerges of analogous effects on peptide length, sequence and affinity of disparate peptidomes, suggesting that similar peptide mediated mechanisms underlie the pathogenesis and the joint contribution of ERAP1/ERAP2 and MHC I to distinct inflammatory diseases. Processing of specific antigens, peptide dependent changes in global properties of the MHC I molecules, such as folding and stability, or both may be pathogenic.
Molecular immunology