title: Proteasome subunits encoded by the major histocompatibility complex are not essential for antigen presentation.
abstract: Major histocompatibility complex (MHC) class I molecules bind and deliver peptides derived from endogenously synthesized proteins to the cell surface for survey by cytotoxic T lymphocytes. It is believed that endogenous antigens are generally degraded in the cytosol, the resulting peptides being translocated into the endoplasmic reticulum where they bind to MHC class I molecules. Transporters containing an ATP-binding cassette encoded by the MHC class II region seem to be responsible for this transport. Genes coding for two subunits of the '20S' proteasome (a multicatalytic proteinase) have been found in the vicinity of the two transporter genes in the MHC class II region, indicating that the proteasome could be the unknown proteolytic entity in the cytosol involved in the generation of MHC class I-binding peptides. By introducing rat genes encoding the MHC-linked transporters into a human cell line lacking both transporter and proteasome subunit genes, we show here that the MHC-encoded proteasome subunit are not essential for stable MHC class I surface expression, or for processing and presentation of antigenic peptides from influenza virus and an intracellular protein.
authors.affiliation: Tumor Immunology Program, German Cancer Research Center, Heidelberg.
authors.forename: F
authors.initials: F
authors.lastname: Momburg
authors.forename: V
authors.initials: V
authors.lastname: Ortiz-Navarrete
authors.forename: J
authors.initials: J
authors.lastname: Neefjes
authors.forename: E
authors.initials: E
authors.lastname: Goulmy
authors.forename: Y
authors.initials: Y
authors.lastname: van de Wal
authors.forename: H
authors.initials: H
authors.lastname: Spits
authors.forename: S J
authors.initials: SJ
authors.lastname: Powis
authors.forename: G W
authors.initials: GW
authors.lastname: Butcher
authors.forename: J C
authors.initials: JC
authors.lastname: Howard
authors.forename: P
authors.initials: P
authors.lastname: Walden
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000818:Animals; D000937:Antigen-Antibody Reactions / Q000502:physiology*; D000956:Antigens, Viral / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology; D015153:Blotting, Western; D002352:Carrier Proteins / Q000502:physiology; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology; D009097:Multienzyme Complexes / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000502:physiology; D051381:Rats; D014162:Transfection; D014763:Viral Matrix Proteins
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000956:Antigens, Viral; D002352:Carrier Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008565:Membrane Proteins; D009097:Multienzyme Complexes; D011506:Proteins; C073119:TAP1 protein, human; C486172:Tap1 protein, rat; C489514:Tap2 protein, rat; D014763:Viral Matrix Proteins; C071692:TAP2 protein, human; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex