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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.

Type

Journal article

Journal

Immunity

Publication Date

01/2000

Volume

12

Pages

107 - 117

Keywords

Antigen Presentation, Antigens, Neoplasm, B-Lymphocytes, Base Sequence, Cell Line, Transformed, Cysteine Endopeptidases, DNA, Complementary, Dendritic Cells, Herpesvirus 4, Human, Humans, Kidney Neoplasms, MART-1 Antigen, Melanoma, Molecular Sequence Data, Multienzyme Complexes, Neoplasm Proteins, Peptides, Proteasome Endopeptidase Complex, Proteins, T-Lymphocytes, Cytotoxic, Tumor Cells, Cultured