Laboratory of Immunogenetics and Tissue Immunology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
Front Immunol. 2022 Jun 13;13:902567. doi: 10.3389/fimmu.2022.902567. eCollection 2022.
To be, or not to be, that is the question. (William Shakespeare, Hamlet) Endoplasmic reticulum aminopeptidases 1 and 2 (ERAP1 and ERAP2, respectively) play a role in trimming peptides that are too long to be bound and presented by class I HLA (HLA-I) molecules to CD8 T cells. They may also affect the HLA-I-presented peptide repertoire by overtrimming potential epitopes. Both enzymes may also be released from the cell to cleave cytokine receptors and regulate blood pressure. Both enzymes are polymorphic, which affects their expression, specificity, and activity, resulting in their role in diseases associated with HLA-I. In this brief review, we concentrate on ERAP2, less investigated because of its lack in laboratory mice and 25% of humans, as well as a lower polymorphism. ERAP2 was found to be associated with several diseases and to influence ERAP1 effects. It was discovered recently that the defective gene, not encoding functional aminopeptidase, may nevertheless, during viral infections, produce a truncated protein isoform of unknown function, possibly interfering with ERAP1 and full-length ERAP2 by heterodimer formation. The disease associations of ERAP2, alone or in combination with ERAP1, are reviewed.
生存还是毁灭，这是个问题。（威廉·莎士比亚，《哈姆雷特》）内质网氨肽酶 1 和 2（分别为 ERAP1 和 ERAP2）在修剪过长而无法与 HLA-I 类分子结合并呈递的肽段方面发挥作用。它们还可能通过过度修剪潜在的表位来影响 HLA-I 呈递的肽库。这两种酶也可能从细胞中释放出来，以切割细胞因子受体并调节血压。这两种酶都是多态性的，这会影响它们的表达、特异性和活性，从而影响它们在与 HLA-I 相关疾病中的作用。在这篇简要综述中，我们集中讨论 ERAP2，因为它在实验室小鼠中缺乏，在 25%的人类中也缺乏，而且多态性较低，所以研究较少。已经发现 ERAP2 与多种疾病有关，并影响 ERAP1 的作用。最近发现，有缺陷的 基因虽然不能编码有功能的氨肽酶，但在病毒感染期间，可能会产生一种未知功能的截短蛋白同工型，通过形成异二聚体，可能会干扰 ERAP1 和全长 ERAP2。我们综述了 ERAP2 单独或与 ERAP1 联合的疾病相关性。
