Class II MHC molecules are present in macrophage lysosomes and phagolysosomes that function in the phagocytic processing of Listeria monocytogenes for presentation to T cells.
Phagocytic processing of heat-killed Listeria monocytogenes by peritoneal macrophages resulted in degradation of these bacteria in phagolysosomal compartments and processing of bacterial antigens for presentation to T cells by class II MHC molecules. Within 20 min of uptake by macrophages, Listeria peptide antigens were expressed on surface class II MHC molecules, capable of stimulating Listeria-specific T cells. Within this period, degradation of labeled bacteria to acid-soluble low molecular weight catabolites also commenced. Immunoelectron microscopy was used to evaluate the compartments involved in this processing. Upon uptake of the bacteria, phagosomes containing Listeria fused rapidly with both lysosomes and endosomes. Class II MHC molecules were present in a tubulo-vesicular lysosome compartment, which appeared to fuse with phagosomes, as well as in the resulting phagolysosomes containing internalized Listeria; these compartments were all positive for Lamp 1 and cathepsin D and lacked 46-kD mannose-6-phosphate receptors. In addition, class II MHC and Lamp 1 were co-localized in vesicles of the trans Golgi reticulum, where they were segregated from 46-kD mannose-6-phosphate receptors. Vesicles containing both Listeria-derived components and class II MHC molecules were also observed; some of these may represent vesicles recycling from phagolysosomes, potentially bearing processed immunogenic peptides complexed with class II MHC. These results support a central role for lysosomes and phagolysosomes in the processing of bacterial antigens for presentation to T cells. Tubulo-vesicular lysosomes appear to represent an important convergence of endocytic, phagocytic and biosynthetic pathways, where antigens may be processed to allow binding to class II MHC molecules and recycling to the cell surface.
Harding
C V
CV
Department of Pathology, Washington University, School of Medicine, St. Louis, Missouri 63110.
Geuze
H J
HJ
D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D002460:Cell Line; D000949:Histocompatibility Antigens Class II / Q000032:analysis / Q000276:immunology*; D006358:Hot Temperature; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis; D007700:Kinetics; D008089:Listeria monocytogenes / Q000276:immunology*; D008247:Lysosomes / Q000276:immunology* / Q000648:ultrastructure; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000648:ultrastructure; D051379:Mice; D008808:Mice, Inbred CBA; D008854:Microscopy, Electron; D008954:Models, Biological; D010587:Phagocytosis; D013601:T-Lymphocytes / Q000276:immunology*
D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D007371:Interferon-gamma