Trimming of peptides by IRAP in endocytic vesicles

While it is established that cathepsin S is involved in antigen processing in endocytotic vesicles, it is less certain whether other proteases present in endocytic vesicles are also involved in generating the peptide fragments. Insulin regulated aminopeptidase (IRAP) is an epitope-trimming zinc-dependent aminopeptidase closely related to ERAP1 and ERAP2. IRAP may be involved in vacuolar processing of the peptide fragments within endosomes (Saveanu et al. 2009, Segura et al. 2009). IRAP is detected predominantly in the early and recycling endosome fractions. Saveanu et al. (2009) observed the physical association of IRAP with internalized class I MHC molecules and suggested that this may favour a direct linkage between peptide trimming and MHC class I loading. They also showed that IRAP-dependent processing of antigens requires active proteasome but not lysosomal proteases, which suggests that this pathway utilizes cytosolic degradation followed by peptide transport into IRAP-containing endosomes.

尽管已知猫蛋白酶S参与内吞体中抗原处理，但对于内吞体中存在的其他蛋白酶是否也参与生成肽片段的产生，其确定性较低。胰岛素调节的氨基肽酶（IRAP）是一种与ERAP1和ERAP2密切相关、依赖于锌的表位修剪氨基肽酶。IRAP可能参与内体中肽片段的溶酶体加工过程（参见Saveanu等人，2009年，Segura等人，2009年）。IRAP主要检测于早期和循环内体组分中。Saveanu等人（2009年）观察到IRAP与内化的I类MHC分子的物理结合，并推测这或许有利于肽修剪与MHC I类加载之间的直接联系。他们还展示了抗原的IRAP依赖性处理需要活性蛋白酶体，而不需要溶酶体蛋白酶，这表明该途径利用细胞质降解，随后将肽转运至含IRAP的内体。