Exogenous antigens are processed through the endoplasmic reticulum-associated degradation (ERAD) in cross-presentation by dendritic cells.
Antigen cross-presentation is critical in infectious and tumor immunity where cytotoxic T lymphocytes are induced by dendritic cells specifically equipped with cellular machineries to present exogenous antigens with major histocompatibility complex (MHC) class I molecules. To examine molecular mechanisms of antigen cross-presentation, we employed as a model system a murine dendritic cell line DC2.4 capable of presenting soluble antigens such as ovalbumin (OVA) with MHC class I. Here, we demonstrate that exogenously added OVA is accumulated in the endoplasmic reticulum (ER) and late endosomes followed by retrograde transport to the cytoplasm through the Sec61 transporter complexes, and that CHIP functions as an E3 ubiquitin-ligase for OVA degradation by proteasomes. This mechanism is essentially the same as that known as the ER-associated degradation (ERAD) in the quality control of secretary and membrane proteins.
Imai
Jun
J
Keio Research Park, Tokyo, Japan.
Hasegawa
Hironori
H
Maruya
Mikako
M
Koyasu
Shigeo
S
Yahara
Ichiro
I
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D045142:Cross-Priming; D003713:Dendritic Cells / Q000737:chemistry / Q000276:immunology*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000032:analysis / Q000276:immunology* / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D034622:RNA Interference; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000502:physiology
D002352:Carrier Proteins; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; C490683:Sec6l1 protein, mouse; D010047:Ovalbumin; C492951:Stub1 protein, mouse; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex