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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.

Original publication

DOI

10.1158/0008-5472.CAN-05-4310

Type

Journal article

Journal

Cancer Res

Publication Date

15/05/2006

Volume

66

Pages

5461 - 5468

Keywords

Animals, Antigen Presentation, Antigens, Neoplasm, Cysteine Endopeptidases, Dendritic Cells, HLA-A2 Antigen, Humans, Immunotherapy, Adoptive, Lymphocyte Activation, MART-1 Antigen, Mice, Mice, Transgenic, Neoplasm Proteins, Proteasome Endopeptidase Complex, T-Lymphocytes, T-Lymphocytes, Cytotoxic