Molecular and pathogenic effects of endoplasmic reticulum aminopeptidases ERAP1 and ERAP2 in MHC-I-associated inflammatory disorders: Towards a unifying view |
| |
Institution: | 1. Department of Dermatology and Venereology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden;2. Rheumatology, Department of Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden;3. Neuroimmunology Unit, Department of Clinical Neurosciences, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden |
| |
Abstract: | 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, Behçet’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. |
| |
Keywords: | ERAP MHC Inflammatory diseases Peptidomics Antigen processing Mechanisms of disease |
本文献已被 ScienceDirect 等数据库收录! |
|