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Two Distinct Pathways Mediated by PA28 and hsp90 in Major Histocompatibility Complex Class I Antigen Processing

Major histocompatibility complex (MHC) class I ligands are mainly produced by the proteasome. Herein, we show that the processing of antigens is regulated by two distinct pathways, one requiring PA28 and the other hsp90. Both hsp90 and PA28 enhanced the antigen processing of ovalbumin (OVA). Geldana...

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Autores principales: Yamano, Taketoshi, Murata, Shigeo, Shimbara, Naoki, Tanaka, Noriaki, Chiba, Tomoki, Tanaka, Keiji, Yui, Katsuyuki, Udono, Heiichiro
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2002
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193925/
https://www.ncbi.nlm.nih.gov/pubmed/12119343
http://dx.doi.org/10.1084/jem.20011922
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author Yamano, Taketoshi
Murata, Shigeo
Shimbara, Naoki
Tanaka, Noriaki
Chiba, Tomoki
Tanaka, Keiji
Yui, Katsuyuki
Udono, Heiichiro
author_facet Yamano, Taketoshi
Murata, Shigeo
Shimbara, Naoki
Tanaka, Noriaki
Chiba, Tomoki
Tanaka, Keiji
Yui, Katsuyuki
Udono, Heiichiro
author_sort Yamano, Taketoshi
collection PubMed
description Major histocompatibility complex (MHC) class I ligands are mainly produced by the proteasome. Herein, we show that the processing of antigens is regulated by two distinct pathways, one requiring PA28 and the other hsp90. Both hsp90 and PA28 enhanced the antigen processing of ovalbumin (OVA). Geldanamycin, an inhibitor of hsp90, almost completely suppressed OVA antigen presentation in PA28α(−/−)/β(−/−) lipopolysaccharide blasts, but not in wild-type cells, indicating that hsp90 compensates for the loss of PA28 and is essential in the PA28-independent pathway. In contrast, treatment of cells with interferon (IFN)-γ, which induces PA28 expression, abrogated the requirement of hsp90, suggesting that IFN-γ enhances the PA28-dependent pathway, whereas it diminishes hsp90-dependent pathway. Importantly, IFN-γ did not induce MHC class I expressions in PA28-deficient cells, indicating a prominent role for PA28 in IFN-γ–stimulated peptide supply. Thus, these two pathways operate either redundantly or specifically, depending on antigen species and cell type.
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spelling pubmed-21939252008-04-11 Two Distinct Pathways Mediated by PA28 and hsp90 in Major Histocompatibility Complex Class I Antigen Processing Yamano, Taketoshi Murata, Shigeo Shimbara, Naoki Tanaka, Noriaki Chiba, Tomoki Tanaka, Keiji Yui, Katsuyuki Udono, Heiichiro J Exp Med Article Major histocompatibility complex (MHC) class I ligands are mainly produced by the proteasome. Herein, we show that the processing of antigens is regulated by two distinct pathways, one requiring PA28 and the other hsp90. Both hsp90 and PA28 enhanced the antigen processing of ovalbumin (OVA). Geldanamycin, an inhibitor of hsp90, almost completely suppressed OVA antigen presentation in PA28α(−/−)/β(−/−) lipopolysaccharide blasts, but not in wild-type cells, indicating that hsp90 compensates for the loss of PA28 and is essential in the PA28-independent pathway. In contrast, treatment of cells with interferon (IFN)-γ, which induces PA28 expression, abrogated the requirement of hsp90, suggesting that IFN-γ enhances the PA28-dependent pathway, whereas it diminishes hsp90-dependent pathway. Importantly, IFN-γ did not induce MHC class I expressions in PA28-deficient cells, indicating a prominent role for PA28 in IFN-γ–stimulated peptide supply. Thus, these two pathways operate either redundantly or specifically, depending on antigen species and cell type. The Rockefeller University Press 2002-07-15 /pmc/articles/PMC2193925/ /pubmed/12119343 http://dx.doi.org/10.1084/jem.20011922 Text en Copyright © 2002, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Yamano, Taketoshi
Murata, Shigeo
Shimbara, Naoki
Tanaka, Noriaki
Chiba, Tomoki
Tanaka, Keiji
Yui, Katsuyuki
Udono, Heiichiro
Two Distinct Pathways Mediated by PA28 and hsp90 in Major Histocompatibility Complex Class I Antigen Processing
title Two Distinct Pathways Mediated by PA28 and hsp90 in Major Histocompatibility Complex Class I Antigen Processing
title_full Two Distinct Pathways Mediated by PA28 and hsp90 in Major Histocompatibility Complex Class I Antigen Processing
title_fullStr Two Distinct Pathways Mediated by PA28 and hsp90 in Major Histocompatibility Complex Class I Antigen Processing
title_full_unstemmed Two Distinct Pathways Mediated by PA28 and hsp90 in Major Histocompatibility Complex Class I Antigen Processing
title_short Two Distinct Pathways Mediated by PA28 and hsp90 in Major Histocompatibility Complex Class I Antigen Processing
title_sort two distinct pathways mediated by pa28 and hsp90 in major histocompatibility complex class i antigen processing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193925/
https://www.ncbi.nlm.nih.gov/pubmed/12119343
http://dx.doi.org/10.1084/jem.20011922
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