Structural requirements for major histocompatibility complex class II invariant chain trafficking in polarized...

The invariant chain (Ii) targets major histocompatibility complex class II molecules to an endocytic processing compartment where they encounter antigenic peptides. Analysis of Ii-transferrin receptor chimeras expressed in polarized Madin-Darby canine kidney (MDCK) cells shows that the Ii cytoplasmic tail contains a dihydrophobic basolateral sorting signal, Met16-Leu17, which is recognized in both the biosynthetic and endocytic pathways. Pro15-Met16-Leu17 has previously been identified as one of two dihydrophobic Ii internalization signals active in non-polarized cells. Pro15 is also required for endocytosis in MDCK cells but not for basolateral sorting, indicating that the internalization signal recognized at the plasma membrane is distinct from the sorting signal recognized by basolateral sorting machinery. Another dihydrophobic sequence, Leu7-Ile8, is required for rapid internalization of the chimeric receptors in MDCK cells but not for basolateral sorting, providing further evidence that the structural requirements for basolateral sorting and internalization differ. Deletion analysis suggests that basolateral sorting of newly synthesized Ii-TR chimeras is also mediated by the membrane-proximal region of the Ii cytoplasmic tail. However, this region does not promote polarized basolateral recycling, indicating that the structural requirements for polarized sorting in the biosynthetic and endocytic pathways are not identical.