Processing of some antigens by the standard proteasome but not by the immunoproteasome results in poor presentation by dendritic cells.
By stimulating human lymphocytes with an autologous renal carcinoma, we obtained CTL recognizing an antigen derived from a novel, ubiquitous protein. The CTL failed to lyse autologous EBV-transformed B cells, even though the latter express the protein. This is due to the presence in these cells of immunoproteasomes, which, unlike standard proteasomes, cannot produce the antigenic peptide. We show that dendritic cells also carry immunoproteasomes and fail to present this antigen. This may explain why the relevant CTL escape thymic deletion and are not regularly activated in the periphery. Lack of cleavage by the immunoproteasome was also observed for melanoma differentiation antigen Melan-A26-35/HLA-A2, currently used for antitumoral vaccination. For immunization with such antigens, proteins should be less suitable than peptides, which do not require proteasome digestion in dendritic cells.
Morel
S
S
Ludwig Institute for Cancer Research, Brussels Branch and Cellular Genetics Unit, Université Catholique de Louvain, Belgium.
Lévy
F
F
Burlet-Schiltz
O
O
Brasseur
F
F
Probst-Kepper
M
M
Peitrequin
A L
AL
Monsarrat
B
B
Van Velthoven
R
R
Cerottini
J C
JC
Boon
T
T
Gairin
J E
JE
Van den Eynde
B J
BJ
D017951:Antigen Presentation / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D002461:Cell Line, Transformed; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000276:immunology*; D018076:DNA, Complementary; D003713:Dendritic Cells / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007680:Kidney Neoplasms / Q000276:immunology; D058965:MART-1 Antigen; D008545:Melanoma / Q000276:immunology; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000276:immunology*; D009363:Neoplasm Proteins / Q000276:immunology; D010455:Peptides / Q000276:immunology; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D018076:DNA, Complementary; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; D010455:Peptides; D011506:Proteins; C071313:LMP-2 protein; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; C098948:PSMB10 protein, human; D046988:Proteasome Endopeptidase Complex