Identifiers
NAME:CLIP*:MHC_class_II*
References
DENDRITIC_CELL
PMID:22076556
The nascent MHC class II protein in the rough ER has its peptide-binding cleft blocked by the invariant chain (Ii; a trimer) to prevent it from binding cellular peptides or peptides from the endogenous pathway. The invariant chain also facilitates MHC class II's export from the ER in a vesicle. The signal for endosomal targeting resides in the cytoplasmic tail of the invariant chain. This fuses with a late endosome containing the endocytosed, degraded proteins. It is then cleaved by cathepsin S (cathepsin L in cortical thymic epithelial cells), leaving only a small fragment called CLIP which blocks peptide binding until HLA-DM binds to MHC II, releasing CLIP and allowing other peptides to bind. The stable MHC class-II is then presented on the cell surface.