Cycling of cell-surface MHC glycoproteins through primaquine-sensitive intracellular compartments.
Class II major histocompatibility complex (MHC) glycoproteins associate with peptides derived from material endocytosed by antigen-presenting cells and processed along the endocytotic pathway. No consensus exists as to what extent class II molecules themselves are endocytosed and it is not known whether endocytosed MHC class II molecules can be recycled again to the cell surface--an itinerary which might allow a single cell-surface MHC molecule to associate with different peptides during its lifetime. We now show by using new cleavable labelling reagents that class II and class I MHC on B lymphoblastoid cells are continually endocytosed and recycled to the cell surface. The intracellular pool size is normally kept small by efficient recycling, but in the presence of primaquine the rate of recycling is slowed, thereby increasing the size of this pool substantially. On removal of the amine, the intracellular population recycles rapidly to restore the original distribution. These results reveal a cycle that might explain the rapid binding and turnover of some peptide/class II MHC complexes and the exchange of pre-existing for new peptides observed in living cells.
Reid
P A
PA
Department of Biochemistry, University of Dundee, UK.
Watts
C
C
D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000276:immunology*; D002794:Choline / Q000031:analogs & derivatives; D004151:Dipeptides; D004591:Electrophoresis, Polyacrylamide Gel; D004705:Endocytosis; D005978:Glutathione / Q000494:pharmacology; D006023:Glycoproteins / Q000378:metabolism*; D004854:Herpesvirus 4, Human; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D007163:Immunosorbent Techniques; D007202:Indicators and Reagents; D007457:Iodine Radioisotopes; D007700:Kinetics; D011319:Primaquine / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D004151:Dipeptides; D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007202:Indicators and Reagents; D007457:Iodine Radioisotopes; C065334:3,3'-dithiopropionyl-1-sulfosuccinimidyl 1'-glycyl-tyrosyl cholamine; D005978:Glutathione; D011319:Primaquine; D002794:Choline