Distinct intracellular compartments involved in invariant chain degradation and antigenic peptide loading of major histocompatibility complex (MHC) class II molecules.
Major histocompatibility complex (MHC) class II molecules are transported to intracellular MHC class II compartments via a transient association with the invariant chain (Ii). After removal of the invariant chain, peptides can be loaded onto class II molecules, a process catalyzed by human leukocyte antigen-DM (HLA-DM) molecules. Here we show that MHC class II compartments consist of two physically and functionally distinct organelles. Newly synthesized MHC class II/Ii complexes were targeted to endocytic organelles lacking HLA-DM molecules, where Ii degradation occurred. From these organelles, class II molecules were transported to a distinct organelle containing HLA-DM, in which peptides were loaded onto class II molecules. This latter organelle was not directly accessible via fluid phase endocytosis, suggesting that it is not part of the endosomal pathway. Uptake via antigen-specific membrane immunoglobulin resulted however in small amounts of antigen in the HLA-DM positive organelles. From this peptide-loading compartment, class II-peptide complexes were transported to the plasma membrane, in part after transit through endocytic organelles. The existence of two separate compartments, one involved in Ii removal and the other functioning in HLA-DM-dependent peptide loading of class II molecules, may contribute to the efficiency of antigen presentation by the selective recruitment of peptide-receptive MHC class II molecules and HLA-DM to the same subcellular location.
Ferrari
G
G
Basel Institute for Immunology, Grenzacherstrasse 487, Basel, Switzerland.
Knight
A M
AM
Watts
C
C
Pieters
J
J
D000907:Antibodies, Bacterial / Q000096:biosynthesis; D002458:Cell Fractionation; D002462:Cell Membrane / Q000276:immunology; D004705:Endocytosis; D011992:Endosomes / Q000276:immunology / Q000648:ultrastructure; D006681:HLA-D Antigens / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis; D007147:Immunoglobulin Light Chains / Q000096:biosynthesis; D008247:Lysosomes / Q000276:immunology / Q000648:ultrastructure; D008545:Melanoma; D015388:Organelles / Q000276:immunology* / Q000648:ultrastructure; D010446:Peptide Fragments / Q000276:immunology; D011994:Recombinant Proteins / Q000032:analysis / Q000096:biosynthesis; D013744:Tetanus Toxin / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured
D000907:Antibodies, Bacterial; D006681:HLA-D Antigens; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D010446:Peptide Fragments; D011994:Recombinant Proteins; D013744:Tetanus Toxin; C040635:tetanus toxin fragment C