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
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U2 - 10.1084/jem.20011922
DO - 10.1084/jem.20011922
M3 - Article
C2 - 12119343
AN - SCOPUS:0037099735
SN - 0022-1007
VL - 196
SP - 185
EP - 196
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 2
ER -