Antigen (Ag)-trimming aminopeptidases belong to the oxytocinase subfamily of M1 metallopeptidases. In humans, this subfamily contains the endoplasmic reticulum aminopeptidases 1 and 2 (ERAP1 and 2) and the insulin-responsive aminopeptidase (IRAP, synonym oxytocinase), an endosomal enzyme. The ability of these enzymes to trim antigenic precursors and to generate major histocompatibility class-I ligands has been demonstrated extensively for ERAP1, less for ERAP2, which is absent in rodents, and exclusively in the context of cross-presentation for IRAP. During 20 years of research on these aminopeptidases, their enzymatic function has been very well characterized and their genetic association with autoimmune diseases, cancers, and infections is well established. The mechanisms by which these proteins are associated to human diseases are not always clear. This review discusses the Ag-trimming-independent functions of the oxytocinase subfamily of M1 aminopeptidases and the new questions raised by recent publications on IRAP and ERAP2.

抗原 (Ag) 修剪氨肽酶属于 M1 金属肽酶催产素酶亚家族。在人类中，该亚家族包含内质网氨肽酶 1 和 2（ERAP1 和 2）以及胰岛素响应性氨肽酶（IRAP，同义词催产素酶）（一种内体酶）。这些酶修剪抗原前体和产生主要组织相容性 I 类配体的能力已在 ERAP1 中得到广泛证实，而在啮齿类动物中不存在的 ERAP2 中得到了较少的证实，并且仅在 IRAP 交叉呈递的情况下得到证实。经过 20 年对这些氨肽酶的研究，它们的酶功能已得到很好的表征，并且它们与自身免疫性疾病、癌症和感染的遗传关联也已得到充分证实。这些蛋白质与人类疾病相关的机制并不总是清楚的。这篇综述讨论了 M1 氨肽酶催产素酶亚家族的 Ag 修饰独立功能以及最近关于 IRAP 和 ERAP2 的出版物提出的新问题。