Puromycin-sensitive aminopeptidase limits MHC class I presentation in dendritic cells but does not affect CD8 T cell responses during viral infections
Authors
Towne, Charles FentonYork, Ian A.
Neijssen, Joost J.
Karow, Margaret L.
Murphy, Andrew J.
Valenzuela, David M.
Yancopoulos, George D.
Neefjes, Jacques J.
Rock, Kenneth L.
UMass Chan Affiliations
Department of PathologyDocument Type
Journal ArticlePublication Date
2008-01-23Keywords
Amino Acid Sequence; Aminopeptidases; Animals; *Antigen Presentation; Antigens, Viral; CD8-Positive T-Lymphocytes; Dendritic Cells; Epitopes; Histocompatibility Antigens Class I; Mice; Mice, Mutant Strains; Molecular Sequence Data; Peptides; Virus Diseases; VirusesLife Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
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.Source
J Immunol. 2008 Feb 1;180(3):1704-12.
DOI
10.4049/jimmunol.180.3.1704Permanent Link to this Item
http://hdl.handle.net/20.500.14038/32880PubMed ID
18209067Related Resources
ae974a485f413a2113503eed53cd6c53
10.4049/jimmunol.180.3.1704