The role of endoplasmic reticulum-associated protein degradation in MHC class I antigen processing.
The processing and presentation of secretory glycoprotein antigens by the MHC class I processing pathway presents an interesting topological problem. That is, how do the luminal glycoprotein antigens gain access to the class I processing machinery located in the cell cytosol? Current data indicate that the retrograde transport of glycoproteins from the endoplasmic reticulum (ER) to cytosol represents the major pathway for ER-associated protein degradation, and most likely represents a major pathway for the processing of glycoprotein antigens by MHC class I molecules as well. There is now a growing list of viral and tumor glycoprotein antigens that undergo retrograde transport from the ER to the cytosol and processing by the ubiquitin-proteasome pathway of degradation. We review here some general aspects of this "ER degradation" pathway, and how it relates to the processing and presentation of class I-associated viral and tumor antigens. In particular, we analyze the role of oligosaccharide trimming and ER molecular chaperones in this process. We would like to emphasize that the class I processing machinery has adapted a common cellular pathway for its use, and that this could lead to the identification of unique characteristics with regard to ER degradation and antigen processing.
Wang
Y
Y
Immunology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA.
Chen
D
D
Androlewicz
M J
MJ
D000818:Animals; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000378:metabolism; D000956:Antigens, Viral / Q000378:metabolism; D001693:Biological Transport, Active; D003546:Cysteine Endopeptidases / Q000378:metabolism; D003600:Cytosol / Q000276:immunology / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000276:immunology* / Q000378:metabolism*; D006023:Glycoproteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D009097:Multienzyme Complexes / Q000378:metabolism; D009844:Oligosaccharides / Q000737:chemistry; D046988:Proteasome Endopeptidase Complex
D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I; D009097:Multienzyme Complexes; D009844:Oligosaccharides; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex