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

59 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

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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