This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chapatte, L. Articles by Lévy, F. Search for Related Content PubMed PubMed Citation Articles by Chapatte, L. Articles by Lévy, F.

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

¹ Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland; ² Ludwig Institute Clinical Trial Center, Columbia University College of Physicians and Surgeons, New York, New York; ³ Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium; ⁴ Department of Biochemistry, University of Lausanne, Epalinges, Switzerland; and ⁵ NCCR, Molecular Oncology, ISREC, Epalinges, Switzerland

Requests for reprints: Frédéric Lévy, Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland. Phone: 41-21-692-59-98; Fax: 41-21-692-59-95; E-mail: frederic.levy{at}isrec.unil.ch.

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. (Cancer Res 2006; 66(10): 5461-8)

This article has been cited by other articles:

				M. Brandes, K. Willimann, G. Bioley, N. Levy, M. Eberl, M. Luo, R. Tampe, F. Levy, P. Romero, and B. Moser Cross-presenting human {gamma}{delta} T cells induce robust CD8+ {alpha}{beta} T cell responses PNAS, February 17, 2009; 106(7): 2307 - 2312. [Abstract] [Full Text] [PDF]

				F. El Hage, V. Stroobant, I. Vergnon, J.-F. Baurain, H. Echchakir, V. Lazar, S. Chouaib, P. G. Coulie, and F. Mami-Chouaib Preprocalcitonin signal peptide generates a cytotoxic T lymphocyte-defined tumor epitope processed by a proteasome-independent pathway PNAS, July 22, 2008; 105(29): 10119 - 10124. [Abstract] [Full Text] [PDF]

				S. M. Walton, M. Gerlinger, O. de la Rosa, N. Nuber, A. Knights, A. Gati, M. Laumer, L. Strauss, C. Exner, N. Schafer, et al. Spontaneous CD8 T Cell Responses against the Melanocyte Differentiation Antigen RAB38/NY-MEL-1 in Melanoma Patients J. Immunol., December 1, 2006; 177(11): 8212 - 8218. [Abstract] [Full Text] [PDF]