The tetraspan protein CD82 is a resident of MHC class II compartments where it associates with HLA-DR, -DM, and -DO molecules.
In specialized APCs, MHC class II molecules are synthesized in the endoplasmic reticulum and transported through the Golgi apparatus to organelles of the endocytic pathway collectively called MHC class II compartments (MIICs). There, the class II-associated invariant chain is degraded, and peptides derived from internalized Ag bind to empty class II in a reaction that is facilitated by the class II-like molecule HLA-DM. An mAb raised to highly purified, immunoisolated MIICs from human B lymphoblastoid cells recognized CD82, a member of the tetraspan family of integral membrane proteins. Subcellular fractionation, immunofluorescence microscopy, and immunoelectron microscopy showed that CD82 is highly enriched in MIICs, particularly in their internal membranes. Coprecipitation analysis showed that CD82 associates in MIICs with class II, DM, and HLA-DO (an inhibitor of peptide loading that binds DM). Similar experiments showed CD63, another tetraspan protein found in MIICs, also associates with these molecules in the compartment and that CD82 and CD63 associate with each other. Preclearing experiments demonstrated that both CD82 and CD63 form complexes with DM-associated class II and DM-associated DO. The ability of CD82 and CD63 to form complexes with class II, DM, and DO in MIICs suggests that the tetraspan proteins may play an important role in the late stages of MHC class II maturation.
Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520-8011, USA.
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Hammond
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Denzin
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Griffith
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Geuze
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Cresswell
D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D001402:B-Lymphocytes; D002451:Cell Compartmentation / Q000276:immunology*; D002461:Cell Line, Transformed; D006681:HLA-D Antigens / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D006367:HeLa Cells; D000949:Histocompatibility Antigens Class II; D006801:Humans; D051861:Kangai-1 Protein; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D011233:Precipitin Tests; D011518:Proto-Oncogene Proteins
D015703:Antigens, CD; C497688:CD82 protein, human; C497689:Cd82 antigen, mouse; C416186:H-2O antigen; C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; C046148:HLA-DO antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D051861:Kangai-1 Protein; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins