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Prepublished online as a Blood First Edition Paper on September 19, 2002; DOI 10.1182/blood-2002-03-0933. This Article Full Text (PDF) All Versions of this Article: 2002-03-0933v1 101/3/1038    most recent 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Consogno, G. Articles by Protti, M. P. Search for Related Content PubMed PubMed Citation Articles by Consogno, G. Articles by Protti, M. P. Social Bookmarking                   What's this? Submitted March 26, 2002 Accepted September 12, 2002 Identification of immunodominant regions among promiscuous HLA-DR restricted CD4+ T cell epitopes on the tumor antigen MAGE-3 Giuseppe Consogno, Simona Manici, Valeria Facchinetti, Angela Bachi, Juergen Hammer, Bianca M Conti-Fine, Claudio Rugarli, Catia Traversari, and Maria Pia Protti* Cancer Immunotherapy and Gene Therapy Program, Scientific Institute H. San Raffaele, Milan, Italy Functional Proteomics HRS-IFOM, Scientific Institute H. San Raffaele, Milan, Italy Department of Genomics and Information Sciences, Hoffmann-La Roche Inc., Nutley, NJ, USA Universita' Vita-Salute San Raffaele, Milan, Italy Cancer Immunotherapy and Gene Therapy Program, Scientific Institute H. San Raffaele, Milan, Italy; MOLMED SpA, Milan, Italy * Corresponding author; email: m.protti{at}hsr.it. The molecular characterization of the CD4+ T cell epitope repertoire on human tumor antigens would contribute to both clinical investigation and cancer immunotherapy. In particular, the identification of promiscuous epitopes would be beneficial to a large number of neoplastic patients regardless of their HLA-DR type. MAGE-3 is a tumor specific antigen widely expressed in solid and hematological malignancies, therefore is an excellent candidate antigen. We used a MHC class II epitope prediction algorithm, the TEPITOPE software, to predict 11 sequence segments of MAGE-3 that could form promiscuous CD4+ T cell epitopes. In binding assays, the synthetic peptides corresponding to the 11 predicted sequences bound at least 3 different HLA-DR alleles. Nine out of the 11 peptides induced proliferation of CD4+ T cells from both healthy subjects and melanoma patients. Four immunodominant regions (residues 111-125, 146-160, 191-205 and 281-295), containing naturally processed epitopes, were recognized by most of the donors, in association with 3 to 4 different HLA-DR alleles, thus covering up to 94% of the alleles expressed in Caucasians. On the contrary, the other promiscuous regions (residues 161-175 and 171-185) contained epitopes not naturally processed in vitro. The immunodominant epitopes identified will be useful in the design of peptide-based cancer vaccines, and in the study of the functional state of tumor specific CD4+ T cells in patients bearing MAGE-3 expressing tumors. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: O. C. Goodyear, G. Pratt, A. McLarnon, M. Cook, K. Piper, and P. 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