Two distinct pathways mediated by PA28 and hsp90 in major histocompatibility complex class I antigen processing

Taketoshi Yamano, Shigeo Murata, Naoki Shimbara, Noriaki Tanaka, Tomoki Chiba, Keiji Tanaka, Katsuyuki Yui, Heiichiro Udono

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

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-/--/- 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.

Original languageEnglish
Pages (from-to)185-196
Number of pages12
JournalJournal of Experimental Medicine
Volume196
Issue number2
DOIs
Publication statusPublished - Jul 15 2002
Externally publishedYes

Fingerprint

Histocompatibility Antigens Class I
Antigen Presentation
Major Histocompatibility Complex
Interferons
Ovalbumin
Proteasome Endopeptidase Complex
Lipopolysaccharides
Ligands
Antigens
Peptides

Keywords

  • Antigen presentation
  • Cytotoxic T lymphocytes
  • Immunity active
  • Macrophage activation
  • Transplantation immunology

ASJC Scopus subject areas

  • Immunology

Cite this

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.

In: Journal of Experimental Medicine, Vol. 196, No. 2, 15.07.2002, p. 185-196.

Research output: Contribution to journalArticle

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. In: Journal of Experimental Medicine. 2002 ; Vol. 196, No. 2. pp. 185-196.
@article{501a1c5fd36b470aaff48eaa6b278805,
title = "Two distinct pathways mediated by PA28 and hsp90 in major histocompatibility complex class I antigen processing",
abstract = "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.",
keywords = "Antigen presentation, Cytotoxic T lymphocytes, Immunity active, Macrophage activation, Transplantation immunology",
author = "Taketoshi Yamano and Shigeo Murata and Naoki Shimbara and Noriaki Tanaka and Tomoki Chiba and Keiji Tanaka and Katsuyuki Yui and Heiichiro Udono",
year = "2002",
month = "7",
day = "15",
doi = "10.1084/jem.20011922",
language = "English",
volume = "196",
pages = "185--196",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "2",

}

TY - JOUR

T1 - Two distinct pathways mediated by PA28 and hsp90 in major histocompatibility complex class I antigen processing

AU - Yamano, Taketoshi

AU - Murata, Shigeo

AU - Shimbara, Naoki

AU - Tanaka, Noriaki

AU - Chiba, Tomoki

AU - Tanaka, Keiji

AU - Yui, Katsuyuki

AU - Udono, Heiichiro

PY - 2002/7/15

Y1 - 2002/7/15

N2 - 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.

AB - 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.

KW - Antigen presentation

KW - Cytotoxic T lymphocytes

KW - Immunity active

KW - Macrophage activation

KW - Transplantation immunology

UR - http://www.scopus.com/inward/record.url?scp=0037099735&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037099735&partnerID=8YFLogxK

U2 - 10.1084/jem.20011922

DO - 10.1084/jem.20011922

M3 - Article

C2 - 12119343

AN - SCOPUS:0037099735

VL - 196

SP - 185

EP - 196

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 2

ER -