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, Maria Pia Protti

Research output: Contribution to journalArticle

Abstract

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 patients with neoplastic diseases regardless of their HLA-DR type. MAGE-3 is a tumor-specific antigen widely expressed in solid and hematologic malignancies; therefore, is an excellent candidate antigen. We used a major histocompatability complex (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 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 whites. 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 tumors expressing MAGE-3.

Original languageEnglish
Pages (from-to)1038-1044
Number of pages7
JournalBlood
Volume101
Issue number3
DOIs
Publication statusPublished - Feb 1 2003

ASJC Scopus subject areas

  • Hematology

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    Consogno, G., Manici, S., Facchinetti, V., Bachi, A., Hammer, J., Conti-Fine, B. M., Rugarli, C., Traversari, C., & Protti, M. P. (2003). Identification of immunodominant regions among promiscuous HLA-DR-restricted CD4+ T-cell epitopes on the tumor antigen MAGE-3. Blood, 101(3), 1038-1044. https://doi.org/10.1182/blood-2002-03-0933