Processing of tumor-associated antigen by the proteasomes of dendritic cells controls in vivo T-cell responses
(2006) Cancer Research — Vol. 66, n° 10, p. 5461-5468 (2006)
Files
CHAPATTE_CR2006.pdf
Restricted Access - Adobe PDF
- 393.04 KB
Details
- Authors
- Abstract
- 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.
- Affiliations
University of Lausanne, Epalinges, Switzerland LICR Lausanne Columbia University College of Physicians and Surgeons, New York (USA) Ludwig Institute Clinical Trial Center University of Lausanne, Epalinges, Switzerland Ludwig Institute Clinical Trial Center University of Lausanne, Epalinges, Switzerland Department of Biochemistry University of Lausanne, Epalinges, Switzerland & ISREC, Epalinges, Switzerland Department of Biochemistry & NCCR, Molecular Oncology University of Lausanne, Epalinges, Switzerland & ISREC, Epalinges, Switzerland LICR Lausanne & NCCR, Molecular Oncology
Citations
Chapatte, L., Ayyoub, M., Morel, S., Peitrequin, A.-L., Lévy, N., Servis, C., Van den Eynde, B., Valmori, D., & Lévy, F. (2006). Processing of tumor-associated antigen by the proteasomes of dendritic cells controls in vivo T-cell responses. Cancer Research, 66(10), 5461-5468. https://doi.org/10.1158/0008-5472.CAN-05-4310 (Original work published 2006)