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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Men, Y. Articles by Romero, P. Search for Related Content PubMed PubMed Citation Articles by Men, Y. Articles by Romero, P.

Assessment of Immunogenicity of Human Melan-A Peptide Analogues in HLA-A*0201/K^b Transgenic Mice¹

Ying Men^*, Isabelle Miconnet^2,*, Danila Valmori, Donata Rimoldi^*, Jean-Charles Cerottini^*, and Pedro Romero^*,

^* Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland; and Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Lausanne Branch, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

Previous studies have shown that substitution of single amino acid residues in human Melan-A immunodominant peptides Melan-A_27–35 and Melan-A_26–35 greatly improved their binding and the stability of peptide/HLA-A*0201 complexes. In particular, one Melan-A peptide analogue was more efficient in the generation of Melan-A peptide-specific and melanoma-reactive CTL than its parental peptide in vitro from human PBL. In this study, we analyzed the in vivo immunogenicity of Melan-A natural peptides and their analogues in HLA-A*0201/K^b transgenic mice. We found that two human Melan-A natural peptides, Melan-A_26–35 and Melan-A_27–35, were relatively weak immunogens, whereas several Melan-A peptide analogues were potent immunogens for in vivo CTL priming. In addition, induced Melan-A peptide-specific mouse CTL cross-recognized natural Melan-A peptides and their analogues. More interestingly, these mouse CTL were also able to lyse human melanoma cell lines in vitro in a HLA-A*0201-restricted, Melan-A-specific manner. Our results indicate that the HLA-A*0201/K^b transgenic mouse is a useful animal model to perform preclinical testing of potential cancer vaccines, and that Melan-A peptide analogues are attractive candidates for melanoma immunotherapy.

This article has been cited by other articles:

				D. Escors, L. Lopes, R. Lin, J. Hiscott, S. Akira, R. J. Davis, and M. K. Collins Targeting dendritic cell signaling to regulate the response to immunization Blood, March 15, 2008; 111(6): 3050 - 3061. [Abstract] [Full Text] [PDF]

				S. Colombetti, T. Fagerberg, P. Baumgartner, L. Chapatte, D. E. Speiser, N. Rufer, O. Michielin, and F. Levy Impact of Orthologous Melan-A Peptide Immunizations on the Anti-Self Melan-A/HLA-A2 T Cell Cross-Reactivity. J. Immunol., June 1, 2006; 176(11): 6560 - 6567. [Abstract] [Full Text] [PDF]

				M. Ayyoub, A. Zippelius, M. J. Pittet, D. Rimoldi, D. Valmori, J.-C. Cerottini, P. Romero, F. Lejeune, D. Lienard, and D. E. Speiser Activation of Human Melanoma Reactive CD8+ T Cells by Vaccination with an Immunogenic Peptide Analog Derived from Melan-A/Melanoma Antigen Recognized by T Cells-1 Clin. Cancer Res., February 1, 2003; 9(2): 669 - 677. [Abstract] [Full Text] [PDF]

				I. Miconnet, S. Koenig, D. Speiser, A. Krieg, P. Guillaume, J.-C. Cerottini, and P. Romero CpG Are Efficient Adjuvants for Specific CTL Induction Against Tumor Antigen-Derived Peptide J. Immunol., February 1, 2002; 168(3): 1212 - 1218. [Abstract] [Full Text] [PDF]

				T. N. J. Bullock, D. W. Mullins, T. A. Colella, and V. H. Engelhard Manipulation of Avidity to Improve Effectiveness of Adoptively Transferred CD8+ T Cells for Melanoma Immunotherapy in Human MHC Class I-Transgenic Mice J. Immunol., November 15, 2001; 167(10): 5824 - 5831. [Abstract] [Full Text] [PDF]

				J.-S. Blanchet, D. Valmori, I. Dufau, M. Ayyoub, C. Nguyen, P. Guillaume, B. Monsarrat, J.-C. Cerottini, P. Romero, and J. E. Gairin A New Generation of Melan-A/MART-1 Peptides That Fulfill Both Increased Immunogenicity and High Resistance to Biodegradation: Implication for Molecular Anti-Melanoma Immunotherapy J. Immunol., November 15, 2001; 167(10): 5852 - 5861. [Abstract] [Full Text] [PDF]

				S. Tangri, G. Y. Ishioka, X. Huang, J. Sidney, S. Southwood, J. Fikes, and A. Sette Structural Features of Peptide Analogs of Human Histocompatibility Leukocyte Antigen Class I Epitopes That Are More Potent and Immunogenic than Wild-Type Peptide J. Exp. Med., September 17, 2001; 194(6): 833 - 846. [Abstract] [Full Text] [PDF]

				T. Luft, M. Rizkalla, T. Y. Tai, Q. Chen, R. I. MacFarlan, I. D. Davis, E. Maraskovsky, and J. Cebon Exogenous Peptides Presented by Transporter Associated with Antigen Processing (TAP)-Deficient and TAP-Competent Cells: Intracellular Loading and Kinetics of Presentation J. Immunol., September 1, 2001; 167(5): 2529 - 2537. [Abstract] [Full Text] [PDF]

				I. Miconnet, I. Coste, F. Beermann, J.-F. Haeuw, J.-C. Cerottini, J.-Y. Bonnefoy, P. Romero, and T. Renno Cancer Vaccine Design: A Novel Bacterial Adjuvant for Peptide-Specific CTL Induction J. Immunol., April 1, 2001; 166(7): 4612 - 4619. [Abstract] [Full Text] [PDF]

				R. P. M. Sutmuller, L. R. H. M. Schurmans, L. M. van Duivenvoorde, J. A. Tine, E. I. H. van der Voort, R. E. M. Toes, C. J. M. Melief, M. J. Jager, and R. Offringa Adoptive T Cell Immunotherapy of Human Uveal Melanoma Targeting gp100 J. Immunol., December 15, 2000; 165(12): 7308 - 7315. [Abstract] [Full Text] [PDF]

				D. Valmori, V. Dutoit, D. Liénard, D. Rimoldi, M. J. Pittet, P. Champagne, K. Ellefsen, U. Sahin, D. Speiser, F. Lejeune, et al. Naturally Occurring Human Lymphocyte Antigen-A2 Restricted CD8+ T-Cell Response to the Cancer Testis Antigen NY-ESO-1 in Melanoma Patients Cancer Res., August 1, 2000; 60(16): 4499 - 4506. [Abstract] [Full Text]

				T. N. J. Bullock, T. A. Colella, and V. H. Engelhard The Density of Peptides Displayed by Dendritic Cells Affects Immune Responses to Human Tyrosinase and gp100 in HLA-A2 Transgenic Mice J. Immunol., March 1, 2000; 164(5): 2354 - 2361. [Abstract] [Full Text] [PDF]

				D. Valmori, F. Levy, I. Miconnet, P. Zajac, G. C. Spagnoli, D. Rimoldi, D. Lienard, V. Cerundolo, J.-C. Cerottini, and P. Romero Induction of Potent Antitumor CTL Responses by Recombinant Vaccinia Encoding a Melan-A Peptide Analogue J. Immunol., January 15, 2000; 164(2): 1125 - 1131. [Abstract] [Full Text] [PDF]

				D. Valmori, J.-F. Fonteneau, S. Valitutti, N. Gervois, R. Dunbar, D. Lienard, D. Rimoldi, V. Cerundolo, F. Jotereau, J.-C. Cerottini, et al. Optimal activation of tumor-reactive T cells by selected antigenic peptide analogues Int. Immunol., December 1, 1999; 11(12): 1971 - 1980. [Abstract] [Full Text] [PDF]

				M. J. Pittet, D. Valmori, P. R. Dunbar, D. E. Speiser, D. Lienard, F. Lejeune, K. Fleischhauer, V. Cerundolo, J.-C. Cerottini, and P. Romero High Frequencies of Naive Melan-a/Mart-1-Specific Cd8+ T Cells in a Large Proportion of Human Histocompatibility Leukocyte Antigen (Hla)-A2 Individuals J. Exp. Med., September 6, 1999; 190(5): 705 - 716. [Abstract] [Full Text] [PDF]