Degradation of cell proteins and the generation of MHC class I-presented peptides.
Major histocompatibility complex (MHC) class I molecules display on the cell surface 8- to 10-residue peptides derived from the spectrum of proteins expressed in the cells. By screening for non-self MHC-bound peptides, the immune system identifies and then can eliminate cells that are producing viral or mutant proteins. These antigenic peptides are generated as side products in the continual turnover of intracellular proteins, which occurs primarily by the ubiquitin-proteasome pathway. Most of the oligopeptides generated by the proteasome are further degraded by distinct endopeptidases and aminopeptidases into amino acids, which are used for new protein synthesis or energy production. However, a fraction of these peptides escape complete destruction and after transport into the endoplasmic reticulum are bound by MHC class I molecules and delivered to the cell surface. Herein we review recent discoveries about the proteolytic systems that degrade cell proteins, how the ubiquitin-proteasome pathway generates the peptides presented on MHC-class I molecules, and how this process is stimulated by immune modifiers to enhance antigen presentation.
Rock
K L
KL
Department of Pathology, University of Massachusetts Medical School, Worcester 01655, USA. Kenneth.Rock@banyan.ummed.edu
Goldberg
A L
AL
D000818:Animals; D017951:Antigen Presentation; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003593:Cytoplasm / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D009097:Multienzyme Complexes / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000276:immunology* / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000276:immunology* / Q000378:metabolism*; D014452:Ubiquitins / Q000276:immunology / Q000378:metabolism
D015395:Histocompatibility Antigens Class I; D009097:Multienzyme Complexes; D010455:Peptides; D011506:Proteins; D014452:Ubiquitins; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex