Melanoma cells present a MAGE-3 epitope to CD4+ cytotoxic T cells in association with histocompatibility leukocyte antigen DR11

Simona Manici, Tiziana Sturniolo, Maria Adele Imro, Juergen Hammer, Francesco Sinigaglia, Christoph Noppen, Giulio Spagnoli, Benedetta Mazzi, Matteo Bellone, Paolo Dellabona, Maria Pia Protti

Research output: Contribution to journalArticle

Abstract

In this study we used TEPITOPE, a new epitope prediction software, to identify sequence segments on the MAGE-3 protein with promiscuous binding to histocompatibility leukocyte antigen (HLA)-DR molecules. Synthetic peptides corresponding to the identified sequences were synthesized and used to propagate CD4+ T cells from the blood of a healthy donor. CD4+ T cells strongly recognized MAGE-3(281-295) and, to a lesser extent, MAGE-3(141-155) and MAGE-3(146-160). Moreover, CD4+ T cells proliferated in the presence of recombinant MAGE-3 after processing and presentation by autologous antigen presenting cells, demonstrating that the MAGE-3 epitopes recognized are naturally processed. CD4+ T cells, mostly of the T helper 1 type, showed specific lyric activity against HLA-DR11/MAGE-3-positive melanoma cells. Cold target inhibition experiments demonstrated indeed that the CD4+ T cells recognized MAGE-3(281-295) in association with HLA-DR11 on melanoma cells. This is the first evidence that a tumor-specific shared antigen forms CD4+ T cell epitopes. Furthermore, we validated the use of algorithms for the prediction of promiscuous CD4+ T cell epitopes, thus opening the possibility of wide application to other tumor-associated antigens. These results have direct implications for cancer immunotherapy in the design of peptide-based vaccines with tumor-specific CD4+ T cell epitopes.

Original languageEnglish
Pages (from-to)871-876
Number of pages6
JournalJournal of Experimental Medicine
Volume189
Issue number5
DOIs
Publication statusPublished - Mar 1 1999

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Keywords

  • CD4 epitopes
  • MAGE-3
  • Melanoma
  • Tumor vaccines adoptive immunotherapy

ASJC Scopus subject areas

  • Immunology

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