title: Antigen secreted from noncytosolic Listeria monocytogenes is processed by the classical MHC class I processing pathway.
abstract: Intracellular bacteria can reside in a vacuolar compartment, or they can escape the vacuole and become free living in the cytoplasm. The presentation of Ag by class I MHC molecules has been defined primarily for Ag present in the cytoplasm. It was therefore thought that Ags from bacteria that remain in a vacuole would not be presented by MHC class I molecules. Although some studies have provided data to support this idea, it is not necessarily true for all intracellular bacteria. For example, we have previously demonstrated that an epitope from the p60 protein secreted by LLO- Listeria monocytogenes, which does not reside in the cytoplasm, can be presented by MHC class I molecules to a T cell clone specific for the epitope, p60217-225. We have further examined the route by which Ag secreted by LLO- L. monocytogenes is presented by MHC class I molecules. Using pharmacological inhibitors, we demonstrate that MHC class I presentation of the p60 epitope derived from by LLO- L. monocytogenes requires phagolysosome fusion and processing by the proteasome. Lysosomal cathepsins, however, are not required for processing of the p60 epitope. Similarly, processing of the AttM epitope, secreted by LLO- L. monocytogenes and presented by H2-M3, also requires phagolysosome fusion and cleavage by the proteasome. Thus, p60 and AttM secreted by LLO- L. monocytogenes are processed via the classical class I pathway for presentation by MHC class I molecules.
authors.affiliation: Division of Basic Immunology, Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206, USA.
authors.forename: H L
authors.initials: HL
authors.lastname: Zwickey
authors.forename: T A
authors.initials: TA
authors.lastname: Potter
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000502:physiology; D000818:Animals; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism; D001427:Bacterial Toxins; D002154:Calpain / Q000502:physiology; D002401:Cathepsin B / Q000502:physiology; D056668:Cathepsin L; D002403:Cathepsins / Q000502:physiology; D003546:Cysteine Endopeptidases / Q000502:physiology; D003600:Cytosol / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D010450:Endopeptidases; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics; D006460:Hemolysin Proteins; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology*; D008247:Lysosomes / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009097:Multienzyme Complexes / Q000502:physiology; D010455:Peptides / Q000276:immunology; D010588:Phagosomes / Q000276:immunology; D046988:Proteasome Endopeptidase Complex
chemical_list: C078516:60 kDa protein, Listeria monocytogenes; D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D000942:Antigens, Bacterial; D000944:Antigens, Differentiation, B-Lymphocyte; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D000939:Epitopes; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D009097:Multienzyme Complexes; D010455:Peptides; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; C486172:Tap1 protein, rat; C045084:invariant chain; D002403:Cathepsins; D010450:Endopeptidases; D002154:Calpain; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L; C534278:Ctsl protein, mouse; C534280:Ctsl protein, rat; C028217:cathepsin S; D046988:Proteasome Endopeptidase Complex; C038705:hlyA protein, Listeria monocytogenes