NDLI: Cytosolic aminopeptidases influence MHC class I-mediated antigen presentation in an allele-dependent manner.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kim, Eunkyung Kwak, Heechun Ahn, Kwangseog
Description	Author Affiliation: Kim E ( National Creative Research Initiative Center for Antigen Presentation, Department of Biological Sciences, Seoul National University, Seoul, Korea.)
Abstract	Antigenic peptides presented by MHC class I molecules are generated mainly by the proteasome in the cytosol. Several cytosolic aminopeptidases further trim proteasomal products to form mature epitopes or individual amino acids. However, the distinct function of cytosolic aminopeptidases in MHC class I Ag processing remains to be elucidated. In this study, we show that cytosolic aminopeptidases differentially affect the cell surface expression of MHC class I molecules in an allele-dependent manner in human cells. In HeLa cells, knockdown of puromycin-sensitive aminopeptidase (PSA) by RNA interference inhibited optimal peptide loading of MHC class I molecules, and their cell surface expression was correspondingly reduced. In contrast, depletion of bleomycin hydrolase (BH) enhanced optimal peptide loading and cell surface expression of MHC class I molecules. We did not find evidence on the effect of leucine aminopeptidase knockdown on the MHC class I Ag presentation. Moreover, we demonstrated that PSA and BH influence the peptide loading and surface expression of MHC class I in an allele-specific manner. In the absence of either PSA or BH, the surface expression and peptide-dependent stability of HLA-A68 were reduced, whereas those of HLA-B15 were enhanced. The surface expression and peptide-dependent stability of HLA-A3 were enhanced by BH knockdown, although those of HLA-B8 were increased in PSA-depleted conditions.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	11
Volume Number	183
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2009-12-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Aminopeptidases Metabolism Antigen Presentation Genetics Cytosol Enzymology Histocompatibility Antigens Class I Alleles Immunology Blotting, Western Flow Cytometry Hela Cells Immunoprecipitation Rna Interference Transfection Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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