title: Molecular and pathogenic effects of endoplasmic reticulum aminopeptidases ERAP1 and ERAP2 in MHC-I-associated inflammatory disorders: Towards a unifying view.
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.
authors: Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid), Madrid, Spain. Electronic address: aldecastro@cbm.csic.es.
authors: José A
authors: JA
authors: López de Castro
authors: Instituto de Inmunología, Facultad de Medicina, Universidad Austral del Chile, Valdivia, Chile; Escuela de Tecnología Médica, Universidad Santo Tomás, Valdivia, Chile.
authors: Carlos
authors: C
authors: Alvarez-Navarro
authors: Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid), Madrid, Spain.
authors: Ariadna
authors: A
authors: Brito
authors: Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid), Madrid, Spain.
authors: Pablo
authors: P
authors: Guasp
authors: Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid), Madrid, Spain.
authors: Adrian
authors: A
authors: Martín-Esteban
authors: Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid), Madrid, Spain.
authors: Alejandro
authors: A
authors: Sanz-Bravo
mesh_terms: D000626:Aminopeptidases / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001528:Behcet Syndrome / Q000235:genetics / Q000276:immunology; D000080365:Birdshot Chorioretinopathy; D002825:Chorioretinitis / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology*; D015778:Minor Histocompatibility Antigens / Q000235:genetics / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000235:genetics / Q000276:immunology; D013167:Spondylitis, Ankylosing / Q000235:genetics / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D015778:Minor Histocompatibility Antigens; D000626:Aminopeptidases; C464841:ERAP1 protein, human; C503944:ERAP2 protein, human
keywords: Antigen processing; ERAP; Inflammatory diseases; MHC; Mechanisms of disease; Peptidomics