Puromycin-sensitive aminopeptidase limits MHC class I presentation in dendritic cells but does not affect CD8 T cell responses during viral infections.
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.
Towne
Charles F
CF
Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
York
Ian A
IA
Neijssen
Joost
J
Karow
Margaret L
ML
Murphy
Andrew J
AJ
Valenzuela
David M
DM
Yancopoulos
George D
GD
Neefjes
Jacques J
JJ
Rock
Kenneth L
KL
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
D000956:Antigens, Viral; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D000626:Aminopeptidases; C025579:enkephalin degrading enzyme