SORTING OF MHC CLASS-II MOLECULES AND THE ASSOCIATED INVARIANT CHAIN-(II) IN POLARIZED MDCK CELLS

Epithelial cells have been found to express MHC class II molecules in vivo and are able to perform class II-restricted antigen presentation. The precise intracellular localization of these molecules in epitheli al cells has been a matter of debate. We have analyzed the polarized t argeting of human MHC class II molecules and the associated invariant chain (Ii) in stably transfected MDCK cells. The class II molecules ar e located at the basolateral surface and in intracellular vesicles, bo th when expressed alone or together with Ii. Ii is located in basolate ral endosomes and can internalize through the basolateral plasma membr ane domain. We show that the cytoplasmic tail of Ii contains informati on for basolateral targeting as it is sufficient to redirect the apica l protein neuraminidase (NA) to the basolateral surface. We find that the two leucine-based motifs (LI and ML) in the cytoplasmic tail of Ii are individually sufficient for endosomal sorting and basolateral tar geting of Ii in MDCK cells. In addition, basolateral sorting informati on is located within the 10 membrane-proximal residues of the Ii cytop lasmic tail. As several different signals mediate basolateral sorting of the class II/Ii complex, a polarized distribution of these molecule s may be an essential feature of antigen presentation in epithelial ce lls.