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A HLA-DQ5 restricted Melan-A/MART-1 epitope presented by melanoma tumor cells to CD4+ T lymphocytes

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Abstract

Melan-A/MART1 is a melanocytic differentiation antigen expressed by tumor cells of the majority of melanoma patients and, as such, is considered as a good target for melanoma immunotherapy. Nonetheless, the number of class I and II restricted Melan-A epitopes identified so far remains limited. Here we describe a new Melan-A/MART-1 epitope recognized in the context of HLA-DQa1*0101 and HLA-DQb1*0501, -DQb1*0502 or -DQb1*0504 molecules by a CD4+ T cell clone. This clone was obtained by in vitro stimulation of PBMC from a healthy donor by the Melan-A51–73 peptide previously reported to contain a HLA-DR4 epitope. The Melan-A51–73 peptide, therefore contains both HLA-DR4 and HLA-DQ5 restricted epitope. We further show that Melan-A51–63 is the minimal peptide optimally recognized by the HLA-DQ5 restricted CD4+ clone. Importantly, this clone specifically recognizes and kills tumor cell lines expressing Melan-A and either HLA-DQb1*0501, -DQb1*0504 or -DQb1*0502 molecules. Moreover, we could detect CD4+ T cells secreting IFN-γ in response to Melan-A51–63 and Melan-A51–73 peptides among tumor infiltrating and blood lymphocytes from HLA-DQ5+ patients. This suggests that spontaneous CD4+ T cell responses against this HLA-DQ5 epitope occur in vivo. Together these data significantly increase the fraction of melanoma patients susceptible to benefit from a Melan-A class II restricted vaccine approach.

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Abbreviations

B-LCL:

B Lymphocyte cell line

pHS:

Pooled human serum

TIL:

Tumor infiltrating lymphocytes

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Acknowledgments

This work was supported by grants from the « Ligue Nationale contre le Cancer » (labelisation 2002–2005).

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Authors and Affiliations

  1. INSERM U601, Institut de biologie, 9 quai moncousu, 44093, Nantes cedex, France

    Pierre Larrieu, Laure-Hélène Ouisse, Yannick Guilloux, Francine Jotereau & Jean-François Fonteneau

  2. Université de Nantes, 44322, Nantes, France

    Yannick Guilloux & Francine Jotereau

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  1. Pierre Larrieu
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  2. Laure-Hélène Ouisse
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  3. Yannick Guilloux
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  5. Jean-François Fonteneau
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Correspondence to Jean-François Fonteneau.

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Larrieu, P., Ouisse, LH., Guilloux, Y. et al. A HLA-DQ5 restricted Melan-A/MART-1 epitope presented by melanoma tumor cells to CD4+ T lymphocytes. Cancer Immunol Immunother 56, 1565–1575 (2007). https://doi.org/10.1007/s00262-007-0300-9

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