IRAP Identifies an Endosomal Compartment Required for MHC Class I Cross-Presentation

Let Me Present to You The presentation of exogenous antigens by major histocompatibility (MHC) class I molecules is referred to as cross-presentation. Cross-presentation by dendritic cells plays a central role in the priming of cytolytic T lymphocyte responses to natural and vaccine antigens and also in the initiation of autoimmune diseases such as type 1 diabetes. A satisfactory cell biological model of cross-presentation is not available, which would be required to decipher the link, inherent in cross-presentation, between the secretory and the endocytic pathways. Saveanu et al. (p. 213 , published online 4 June) identify an aminopeptidase, insulin-regulated aminopeptidase (IRAP), which interacts directly with MHC class I molecules. IRAP plays an exclusive and important role in MHC class I cross-presentation of receptor-targeted and phagocytosed antigens. In particular, a specific endosomal compartment, which carries IRAP as a unique marker, is implicated in cross-presentation of phagocytosed antigens.