EXON-6 IS ESSENTIAL FOR INVARIANT CHAIN TRIMERIZATION AND INDUCTION OF LARGE ENDOSOMAL STRUCTURES

Invariant chain (Ii) is a transmembrane type II protein that forms a c omplex with the major histocompatibility complex (MHC) class II molecu les in the endoplasmic reticulum (ER). The membrane proximal luminal r egion of Ii is responsible for the non-covalent association with MHC c lass II molecules. Chemical cross-linking in COS cells was used to stu dy the effect of luminal and cytoplasmic deletions on trimerization of Ii. We demonstrate that trimerization of Ii is independent of the cyt osolic tail of Ii, whereas residues 162-191 (the sequence encoded by e xon 6) in the luminal part of Ii are essential for trimer formation. I mmunofluorescence studies of the transfected luminal deletion construc ts show that the amino acids encoded by exon 6 of Ii are also essentia l for the induction of large endosomal vesicles. The data suggest that Ii must be in a trimeric form to modify the endosomal pathway.