Processing of Tumor-Associated Antigen by the Proteasomes of Dendritic Cells Controls In vivo T-Cell Responses

Chapatte L, Ayyoub M, Morel S, Peitrequin AL, Levy N, Servis C, Van den Eynde BJ, Valmori D, Levy F
Source: Cancer Res
Publication Date: (2006)
Issue: 66(10): 5461-8
Research Area:
Cancer Research/Cell Biology
Immunotherapy / Hematology
Cells used in publication:
Dendritic cell (NHDC), human
Species: human
Tissue Origin: blood
Nucleofector® I/II/2b
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.