Molecular and pathogenic effects of endoplasmic reticulum aminopeptidases ERAP1 and ERAP2 in MHC-I-associated inflammatory disorders: Towards a unifying view

Mol Immunol. 2016 Sep;77:193-204. doi: 10.1016/j.molimm.2016.08.005. Epub 2016 Aug 11.

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: Antigen processing; ERAP; Inflammatory diseases; MHC; Mechanisms of disease; Peptidomics.

Publication types

  • Review

MeSH terms

  • Aminopeptidases / genetics
  • Aminopeptidases / immunology*
  • Animals
  • Behcet Syndrome / genetics
  • Behcet Syndrome / immunology
  • Birdshot Chorioretinopathy
  • Chorioretinitis / genetics
  • Chorioretinitis / immunology
  • Genetic Predisposition to Disease
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Inflammation / genetics
  • Inflammation / immunology*
  • Minor Histocompatibility Antigens / genetics
  • Minor Histocompatibility Antigens / immunology*
  • Polymorphism, Single Nucleotide
  • Psoriasis / genetics
  • Psoriasis / immunology
  • Spondylitis, Ankylosing / genetics
  • Spondylitis, Ankylosing / immunology

Substances

  • Histocompatibility Antigens Class I
  • Minor Histocompatibility Antigens
  • Aminopeptidases
  • ERAP1 protein, human
  • ERAP2 protein, human

Supplementary concepts

  • Birdshot chorioretinopathy