Proteasome subunits encoded in the MHC are not generally required for the processing of peptides bound by MHC class I molecules.
Antigen processing provides major histocompatibility complex (MHC) class I molecules with short peptides, which they selectively bind and present to cytotoxic T lymphocytes. The proteolytic system generating these peptides in the cytosol is unidentified, but their delivery into the endoplasmic reticulum is mediated by the TAP1-TAP2 transporter encoded in the MHC class II region. Closely linked to TAP1 and TAP2 are genes for the LMP2 and LMP7 proteins, which resemble components of proteasomes, proteolytic complexes known to degrade cytosolic proteins. This association has led to the common assumption that proteasomes function in this immunological pathway (discussed in ref. 15). We now show that the expression of stably assembled class I molecules and apparently normal peptide processing can be completely restored in the absence of LMP2 and LMP7 in the human lymphoblastoid cell line mutant 721.174 (refs 16, 17). The identity of LMP7 is directly confirmed by reconstitution of a proteasomal subunit after gene transfer. These results therefore dispute the hypothetical involvement of proteasomes in antigen processing, although a more subtle effect of LMP2 and LMP7 cannot be ruled out.
Arnold
D
D
Division of Tumor Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Driscoll
J
J
Androlewicz
M
M
Hughes
E
E
Cresswell
P
P
Spies
T
T
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000937:Antigen-Antibody Reactions / Q000502:physiology*; D000956:Antigens, Viral / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D003546:Cysteine Endopeptidases; D015180:Electrophoresis, Gel, Two-Dimensional; D015234:HLA-A Antigens / Q000378:metabolism; D015235:HLA-B Antigens / 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; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D014763:Viral Matrix Proteins
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; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008565:Membrane Proteins; D009097:Multienzyme Complexes; D011506:Proteins; C073119:TAP1 protein, human; D014763:Viral Matrix Proteins; C071692:TAP2 protein, human; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex