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

The Journal of Immunology : Official Journal of the American Association of Immunologists
Eunkyung KimKwangseog Ahn

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 thos...Continue Reading

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Citations

Oct 5, 2011·Molecular & Cellular Proteomics : MCP·Noel García-MedelJosé A López de Castro
Sep 17, 2013·PloS One·Jiangan XieHu Mei
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Jun 19, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sabrina UrbanUlrike Seifert
Jan 16, 2018·Clinical & Translational Immunology·Zhixiu Li, Matthew A Brown

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