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Selective identification of HLA-DP4 binding T cell epitopes encoded by the MAGE-A gene family

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Abstract

Because of the high frequency of HLA-DP4 in the Caucasian population, we have selectively delineated HLA-DP4 restricted T cell epitopes in the MAGE-A tumor antigens. We identified 12 good binders to HLA-DP4 and investigated the capacity of the seven best binders to induce in vitro specific CD4+ T cell lines from HLA-DP4 healthy donors. We found that the MAGE-A1 90–104 peptide exhibited a high and constant frequency of CD4+ T cell precursors in all the six tested donors. The MAGE-A1 268–282 peptide was found immunogenic in only two donors but with a high precursor frequency. The MAGE-A12 127–141 peptide was T cell stimulating in six different donors and induced fewer T cell lines. The peptide-specific T cell lines were stimulated by DC loaded with the lysates of cells transfected with MAGE-A1 or MAGE-A12, or loaded with the recombinant protein. We also show that the immunoreactivity of CD4+ T cell epitopes restricted to the same HLA II molecule may vary from one individual to another, as a result of inter-individual variations in the CD4+ T cell repertoire.

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Acknowledgments

This work was supported by the CEA (BM), a grant from Association pour la Recherche contre le Cancer (ARC) (BM), National Institutes of Health (NIH)/ National Cancer Institute (NCI) Grants CA90360 (HZ and BM) and CA112198 (HZ).

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Authors and Affiliations

  1. Protein Engineering and Research Department, CEA-Saclay, 91191, Gif sur Yvette, France

    Xiao-Fei Wang, William M. Cohen, Florence A. Castelli, Christine Almunia, Sandra Pouvelle-Moratille, Gaetan Munier, André Ménez & Bernard Maillère

  2. Ludwig Institute for Cancer Research and Cellular Genetics Unit, Université Catholique de Louvain, 74 avenue Hippocrate, UCL 74.59, 1200, Brussels, Belgium

    Bernard Lethé & Pierre van der Bruggen

  3. INSERM U662, Hôpital St Louis, 75475, Paris cedex 10, France

    Dominique Charron & Marc Busson

  4. Department of Medicine and Division of Hematology/Oncology, Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, France

    Hassan M. Zarour

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  1. Xiao-Fei Wang
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  2. William M. Cohen
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  3. Florence A. Castelli
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Correspondence to Bernard Maillère.

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Wang, XF., Cohen, W.M., Castelli, F.A. et al. Selective identification of HLA-DP4 binding T cell epitopes encoded by the MAGE-A gene family. Cancer Immunol Immunother 56, 807–818 (2007). https://doi.org/10.1007/s00262-006-0230-y

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  • DOI: https://doi.org/10.1007/s00262-006-0230-y

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