Article: article from journal or magazin.
Processing of tumor-associated antigen by the proteasomes of dendritic cells controls in vivo T-cell responses.
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Dendritic cells are unique in their capacity to process antigens and prime naive CD8(+) T cells. Contrary to most cells, which express the standard proteasomes, dendritic cells express immunoproteasomes constitutively. The melanoma-associated protein Melan-A(MART1) contains an HLA-A2-restricted peptide that is poorly processed by melanoma cells expressing immunoproteasomes in vitro. Here, we show that the expression of Melan-A in dendritic cells fails to elicit T-cell responses in vitro and in vivo because it is not processed by the proteasomes of dendritic cells. In contrast, dendritic cells lacking immunoproteasomes induce strong anti-Melan-A T-cell responses in vitro and in vivo. These results suggest that the inefficient processing of self-antigens, such as Melan-A, by the immunoproteasomes of professional antigen-presenting cells prevents the induction of antitumor T-cell responses in vivo.
Animals, Antigen Presentation/immunology, Antigens, Neoplasm, Cysteine Endopeptidases/biosynthesis, Cysteine Endopeptidases/immunology, Dendritic Cells/enzymology, Dendritic Cells/immunology, HLA-A2 Antigen/immunology, Humans, Immunotherapy, Adoptive/methods, Lymphocyte Activation, Mice, Mice, Transgenic, Neoplasm Proteins/immunology, Neoplasm Proteins/metabolism, Proteasome Endopeptidase Complex/immunology, T-Lymphocytes/immunology, T-Lymphocytes, Cytotoxic/immunology
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