Cattedra di Immunologia, Dipartimento di Scienze Biomediche e Cliniche L. Sacco", Università degli Studi di Milano, 20157 Milan, Italy.
Cattedra di Immunologia, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti Università degli Studi di Milano, 20122 Milan, Italy.
Cells. 2020 Mar 14;9(3):720. doi: 10.3390/cells9030720.
Endoplasmic reticulum (ER) aminopeptidases ERAP1 and ERAP2 (ERAPs) are crucial enzymes shaping the major histocompatibility complex I (MHC I) immunopeptidome. In the ER, these enzymes cooperate in trimming the N-terminal residues from precursors peptides, so as to generate optimal-length antigens to fit into the MHC class I groove. Alteration or loss of ERAPs function significantly modify the repertoire of antigens presented by MHC I molecules, severely affecting the activation of both NK and CD8 T cells. It is, therefore, conceivable that variations affecting the presentation of pathogen-derived antigens might result in an inadequate immune response and onset of disease. After the first evidence showing that ERAP1-deficient mice are not able to control Toxoplasma gondii infection, a number of studies have demonstrated that ERAPs are control factors for several infectious organisms. In this review we describe how susceptibility, development, and progression of some infectious diseases may be affected by different ERAPs variants, whose mechanism of action could be exploited for the setting of specific therapeutic approaches.
内质网氨肽酶 ERAP1 和 ERAP2（ERAPs）是塑造主要组织相容性复合体 I（MHC I）免疫肽组的关键酶。在 ER 中，这些酶合作从前体肽中修剪 N 末端残基，从而产生最佳长度的抗原以适合 MHC I 槽。ERAPs 功能的改变或丧失会显著改变 MHC I 分子呈递的抗原谱，严重影响 NK 和 CD8 T 细胞的激活。因此，可以想象，影响病原体衍生抗原呈递的变异可能导致免疫反应不足和疾病发作。在首次证明 ERAP1 缺陷小鼠无法控制弓形虫感染的证据后，许多研究表明 ERAPs 是几种感染性生物体的控制因素。在这篇综述中，我们描述了不同 ERAPs 变体如何影响某些传染病的易感性、发展和进展，其作用机制可用于制定特定的治疗方法。
