A segment of the MHC class II β chain plays a critical role in targeting class II molecules to the endocytic pathway

ability of MHC class II molecules to sort into the endocytic pathway has generally been attributed to the invariant chain glycoproteln. In this paper, we present evidence suggesting that lumenal sequence in the MHC class II molecule itself control the post-Goigi entry of class II into endosomes. Single amlno acid changes have been introduced into a highly conserved region of the class II β chain (amino acids 80–83). Mutant class II β chain genes and wild-type α chain genes have been transfected into cells that lack both class II and invariant chain expression. Immunofluorescent staining of transfected cells indicates that single amino acid changes in this region of β can positively or negatively modulate expression of class II in endocytic vesicles Independently of invariant chain. Mutation at residue 80 leads to prominent localization in vesicular structures typical of late endocytic compartments, while a change at position 82 leads to arrest in the Goigi. 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.