Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid), Madrid, Spain.
Mol Immunol. 2014 Jan;57(1):12-21. doi: 10.1016/j.molimm.2013.06.012. Epub 2013 Jul 31.
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. ERAP1 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.
内质网氨肽酶 1（ERAP1）是一种多功能酶，参与主要组织相容性复合体 I 类（MHC-I）配体的最终加工，对 MHC-I 蛋白的稳定性和免疫特性有重要影响。ERAP1 多态性与 HLA-B27 阳性个体中的强直性脊柱炎有关，天然变异体的改变酶活性对 HLA-B27 肽组有显著影响，提示肽在这种疾病中的关键致病作用。同样，ERAP1 与其他 MHC-I 相关疾病的关联及其与易感性 MHC 等位基因的上位性表明 MHC-I 肽组在这些疾病中具有普遍作用。ERAP1 与 HLA-B27 或其他 MHC-I 分子之间的功能相互作用可能与特定表位的加工有关，或者与更普遍的依赖肽对 MHC-I 蛋白其他生物学特性的影响有关。此外，考虑到 ERAP1 的报告功能，包括其参与血管生成和巨噬细胞激活，不能排除其在这些疾病中炎症和免疫途径中更复杂和多层次的影响。
