title: Puromycin-sensitive aminopeptidase limits MHC class I presentation in dendritic cells but does not affect CD8 T cell responses during viral infections.
abstract: Previous experiments using enzyme inhibitors, cell lysates, and purified enzyme have suggested that puromycin-sensitive aminopeptidase (PSA) plays a role in creating and destroying MHC class I-presented peptides although its precise contribution to these processes is unknown. To examine the importance of this enzyme in MHC class I Ag presentation, we have generated PSA-deficient mice and cell lines from these animals. PSA-deficient mice are smaller and do not reproduce as well as wild type mice. In addition, dendritic cells from PSA-deficient mice display more MHC class I molecules on the cell surface, suggesting that PSA normally limits Ag presentation by destroying certain peptides in these key APCs. Surprisingly, MHC class I levels are not altered on other PSA-deficient cells and the processing and presentation of peptide precursors in PSA-deficient fibroblasts is normal. Moreover, PSA-deficient mice have normal numbers of T cells in the periphery, and respond as well as wild type mice to eight epitopes from three viruses. These data indicate that PSA may play a role in limiting MHC class I Ag presentation in dendritic cells in vivo but that it is not essential for generating most MHC class I-presented peptides or for stimulating CTL responses to several Ags.
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
authors.forename: Charles F
authors.initials: CF
authors.lastname: Towne
authors.forename: Ian A
authors.initials: IA
authors.lastname: York
authors.forename: Joost
authors.initials: J
authors.lastname: Neijssen
authors.forename: Margaret L
authors.initials: ML
authors.lastname: Karow
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Murphy
authors.forename: David M
authors.initials: DM
authors.lastname: Valenzuela
authors.forename: George D
authors.initials: GD
authors.lastname: Yancopoulos
authors.forename: Jacques J
authors.initials: JJ
authors.lastname: Neefjes
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Rock
mesh_terms: D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000235:genetics / Q000502:physiology*; D000818:Animals; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology; D014780:Viruses / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D000626:Aminopeptidases; C025579:enkephalin degrading enzyme