A SEGMENT OF THE MHC CLASS-II BETA-CHAIN PLAYS A CRITICAL ROLE IN TARGETING CLASS-II MOLECULES TO THE ENDOCYTIC PATHWAY

The ability of MHC class II molecules to sort into the endocytic pathw ay has generally been attributed to the invariant chain glycoprotein. In this paper, we present evidence suggesting that lumenal sequences i n the MHC class II molecule itself control the post-Golgi entry of cla ss II into endosomes. Single amino acid changes have been introduced i nto a highly conserved region of the class II beta chain (amino acids 80-83). Mutant class II beta chain genes and wild-type alpha chain gen es have been transfected into cells that lack both class II and invari ant chain expression. immunofluorescent staining of transfected cells indicates that single amino acid changes in this region of beta can po sitively or negatively modulate expression of class II in endocytic ve sicles independently of invariant chain. Mutation at residue 80 leads to prominent localization in vesicular structures typical of late endo cytic compartments, while a change at position 82 leads to arrest in t he Golgi. These data argue in favor of the possibility that MHC class II molecules bear a sorting signal that allows access to MHC class II molecules into the endocytic pathway of antigen presenting cells.