HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services 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 Chapiro, J. Articles by Van den Eynde, B. J. Search for Related Content PubMed PubMed Citation Articles by Chapiro, J. Articles by Van den Eynde, B. J.

Destructive Cleavage of Antigenic Peptides Either by the Immunoproteasome or by the Standard Proteasome Results in Differential Antigen Presentation¹

Jacques Chapiro^*, Stéphane Claverol^2,, Fanny Piette^*, Wenbin Ma^*, Vincent Stroobant^*, Benoît Guillaume^*, Jean-Edouard Gairin^3,, Sandra Morel^4,*, Odile Burlet-Schiltz, Bernard Monsarrat, Thierry Boon^* and Benoît J. Van den Eynde^5,*

^* Ludwig Institute for Cancer Research, Brussels Branch, and Cellular Genetics Unit, Université Catholique de Louvain (UCL), Brussels, Belgium; and Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique, Toulouse, France

The immunoproteasome (IP) is usually viewed as favoring the production of antigenic peptides presented by MHC class I molecules, mainly because of its higher cleavage activity after hydrophobic residues, referred to as the chymotrypsin-like activity. However, some peptides have been found to be better produced by the standard proteasome. The mechanism of this differential processing has not been described. By studying the processing of three tumor antigenic peptides of clinical interest, we demonstrate that their differential processing mainly results from differences in the efficiency of internal cleavages by the two proteasome types. Peptide gp100_209–217 (ITDQVPSFV) and peptide tyrosinase_369–377 (YMDGTMSQV) are destroyed by the IP, which cleaves after an internal hydrophobic residue. Conversely, peptide MAGE-C2_336–344 (ALKDVEERV) is destroyed by the standard proteasome by internal cleavage after an acidic residue, in line with its higher postacidic activity. These results indicate that the IP may destroy some antigenic peptides due to its higher chymotrypsin-like activity, rather than favor their production. They also suggest that the sets of peptides produced by the two proteasome types differ more than expected. Considering that mature dendritic cells mainly contain IPs, our results have implications for the design of immunotherapy strategies.

This article has been cited by other articles:

				K. Hallermalm, K. Seki, A. De Geer, B. Motyka, R. C. Bleackley, M. J. Jager, C. J. Froelich, R. Kiessling, V. Levitsky, and J. Levitskaya Modulation of the Tumor Cell Phenotype by IFN-{gamma} Results in Resistance of Uveal Melanoma Cells to Granule-Mediated Lysis by Cytotoxic Lymphocytes J. Immunol., March 15, 2008; 180(6): 3766 - 3774. [Abstract] [Full Text] [PDF]

				J. Dannull, D.-T. Lesher, R. Holzknecht, W. Qi, G. Hanna, H. Seigler, D. S. Tyler, and S. K. Pruitt Immunoproteasome down-modulation enhances the ability of dendritic cells to stimulate antitumor immunity Blood, December 15, 2007; 110(13): 4341 - 4350. [Abstract] [Full Text] [PDF]

				M. Marcilla, J. J. Cragnolini, and J. A. Lopez de Castro Proteasome-independent HLA-B27 Ligands Arise Mainly from Small Basic Proteins Mol. Cell. Proteomics, May 1, 2007; 6(5): 923 - 938. [Abstract] [Full Text] [PDF]

				M. D. Robek, M. L. Garcia, B. S. Boyd, and F. V. Chisari Role of Immunoproteasome Catalytic Subunits in the Immune Response to Hepatitis B Virus J. Virol., January 15, 2007; 81(2): 483 - 491. [Abstract] [Full Text] [PDF]

				A. O. Weinzierl, C. Lemmel, O. Schoor, M. Muller, T. Kruger, D. Wernet, J. Hennenlotter, A. Stenzl, K. Klingel, H.-G. Rammensee, et al. Distorted Relation between mRNA Copy Number and Corresponding Major Histocompatibility Complex Ligand Density on the Cell Surface Mol. Cell. Proteomics, January 1, 2007; 6(1): 102 - 113. [Abstract] [Full Text] [PDF]

				K. C. Pang, M. T. Sanders, J. J. Monaco, P. C. Doherty, S. J. Turner, and W. Chen Immunoproteasome Subunit Deficiencies Impact Differentially on Two Immunodominant Influenza Virus-Specific CD8+ T Cell Responses J. Immunol., December 1, 2006; 177(11): 7680 - 7688. [Abstract] [Full Text] [PDF]