title: The proteasome inhibitor lactacystin prevents the generation of an endoplasmic reticulum leader-derived T cell epitope.
abstract: The presentation of viral antigens on MHC class I molecules requires their intracellular fragmentation into peptides of appropriate length and anchor residue positions. Evidence has accumulated that the proteasome is the endoprotease in charge of the generation of MHC class I ligands in the cytoplasm. The generation of T cell epitopes derived from the leader peptides of endoplasmic reticulum (ER) targeted proteins, however. has been reported to be independent of the proteasome. Here we show that the H-2Db restricted antigen presentation of the immunodominant T cell epitope derived from the ER leader of the glycoprotein of lymphocytic choriomeningitis virus (LCMV) is completely abolished by administration of the proteasome inhibitor lactacystin. Thus our data support the role of the proteasome in class I restricted antigen processing and extend it to an ER leader derived epitope from a viral glycoprotein.
authors.affiliation: Institute of Experimental Immunology, Department of Pathology, University of Zürich, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Gallimore
authors.forename: K
authors.initials: K
authors.lastname: Schwarz
authors.forename: M
authors.initials: M
authors.lastname: van den Broek
authors.forename: H
authors.initials: H
authors.lastname: Hengartner
authors.forename: M
authors.initials: M
authors.lastname: Groettrup
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects* / Q000502:physiology; D000956:Antigens, Viral / Q000276:immunology / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D003864:Depression, Chemical; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism*; D006183:H-2 Antigens / Q000276:immunology; D064532:Histocompatibility Antigen H-2D; D016056:Immunodominant Epitopes / Q000276:immunology / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009097:Multienzyme Complexes / Q000378:metabolism*; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D021382:Protein Sorting Signals / Q000276:immunology / Q000378:metabolism*; D014764:Viral Proteins
chemical_list: D000956:Antigens, Viral; D004791:Enzyme Inhibitors; D006023:Glycoproteins; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D016056:Immunodominant Epitopes; D036341:Intercellular Signaling Peptides and Proteins; D009097:Multienzyme Complexes; D010446:Peptide Fragments; D021382:Protein Sorting Signals; D014764:Viral Proteins; C094244:glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus; C115679:glycoprotein peptide, Lymphocytic choriomeningitis virus; C115680:glycoprotein peptide, SGVENPGGYCL; C067713:lactacystin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D000111:Acetylcysteine