Av. Chervonsky et al., A SEGMENT OF THE MHC CLASS-II BETA-CHAIN PLAYS A CRITICAL ROLE IN TARGETING CLASS-II MOLECULES TO THE ENDOCYTIC PATHWAY, International immunology, 6(7), 1994, pp. 973-982
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.