ERAP1 structure, function and pathogenetic role in ankylosing spondylitis and other MHC-associated diseases

作者：Alvarez Navarro Carlos; Lopez de Castro Jose A

来源：Molecular Immunology, 2014, 57(1): 12-21.

DOI：10.1016/j.molimm.2013.06.012

• ERAPI
• Aminopeptidases
• Ankylosing spondylitis
• HLA-B27
• Spondyloarthropathies
• Antigen processing

The endoplasmic reticulum aminopeptidase 1 (ERAP1) is a multifunctional enzyme involved in the final processing of Major Histocompatibility Complex class I (MHC-I) ligands and with a significant influence in the stability and immunological properties of MHC-I proteins. ERAPI polymorphism is associated with ankylosing spondylitis among HLA-B27-positive individuals and the altered enzymatic activity of natural variants has significant effects on the HLA-B27 peptidome, suggesting a critical pathogenetic role of peptides in this disease. Likewise, the association of ERAP1 with other MHC-I associated disorders and its epistasis with their susceptibility MHC alleles point out to a general role of the MHC-I peptidome in these diseases. The functional interaction between ERAP1 and HLA-B27 or other MHC-I molecules may be related to the processing of specific epitopes, or to a more general peptide-dependent influence on other biological features of the MHC-I proteins. In addition, from a consideration of the reported functions of ERAP1, including its involvement in angiogenesis and macrophage activation, a more complex and multi-level influence in the inflammatory and immune pathways operating in these diseases cannot be ruled out.

• 出版日期2014-1