EFFICIENT ENDOSOMAL LOCALIZATION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS II-INVARIANT CHAIN COMPLEXES REQUIRES MULTIMERIZATION OF THE INVARIANT CHAIN TARGETING SEQUENCE

During biosynthesis, MHC class II-invariant chain complexes are transp orted into endosomal compartments where invariant chain (Ii) is degrad ed and class II encounters antigenic peptides. One of the signals that determines this intracellular transport route has been localized to t he cytosolic domain of Ii, Deletion of this signal disrupts endosomal targeting and results in the stable expression of class II-Ii complexe s at the surface, In this paper we have examined the role of Ii trimer ization on the generation of this endosomal localization signal. In L cell transfectants expressing class II and both wild type Ii and a tru ncated form of Ii that lacks this endosomal localization signal, Ii wa s found to form multimers which could contain both wild type and trunc ated Ii. The multimers were not large aggregates but were found to be discrete complexes, probably the nine molecule class II-Ii complex tha t has been observed in human B cells. The co-expression of truncated I i allowed for cell surface expression of a subset of wild type Ii. Thi s surface-expressed wild type Ii associated with truncated Ii in multi mers at a 2:1 ratio, indicating that these trimers contain two truncat ed and one wild type Ii molecule. These data suggest a division in tra fficking of Ii trimers: if two wild type Ii molecules are present, the complex is transported to and rapidly degraded in endosomes, whereas the presence of only one wild type Ii results in trafficking and expre ssion of the heterotrimer on the cell surface, Following surface arriv al, complexes containing only a single wild type Ii molecule are inter nalized more rapidly and have a shorter half-life than complexes conta ining only truncated Ii molecules. These data suggest that although a single Ii cytosolic domain can function as a plasma membrane internali zation signal, multimerization of Ii is required for efficient Golgi c omplex to endosome targeting of class II-II complexes.