Identification of two Melan-A CD4+ T cell epitopes presented by frequently expressed MHC class II alleles

Clin Immunol. 2006 Oct;121(1):54-62. doi: 10.1016/j.clim.2006.05.007. Epub 2006 Jun 30.

Abstract

Because of its expression pattern restricted to cells of the melanocytic lineage and to melanoma cells, Melan-A is an important target of immunotherapeutic approaches for the treatment of melanoma. Identification of Melan-A derived sequences recognized by specific T cells is therefore of great interest for the development of these therapeutic strategies. Using circulating CD4(+) T cells from healthy donors, we identified two Melan-A-derived CD4(+) T cell epitopes mapping to the 1-20 and 91-110 regions of the protein and restricted by HLA-DR11 and HLA-DR52 molecules, respectively. CD4(+) T cells specific for the identified epitopes were able to recognize the native antigen when endogenously expressed by antigen presenting cells and tumor cells. In addition, CD4(+) T cells specific for Melan-A 91-110 recognized the epitope after exogenous processing and presentation of Melan-A recombinant protein. Identification of these epitopes will be instrumental for the evaluation of the immune response to Melan-A in cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / metabolism*
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Line, Transformed
  • Cell Line, Tumor
  • Clone Cells
  • Epitopes, T-Lymphocyte / immunology
  • Epitopes, T-Lymphocyte / metabolism*
  • HLA-DR Antigens / immunology
  • HLA-DR Antigens / metabolism
  • HLA-DR Serological Subtypes
  • HLA-DR5 Antigen / immunology
  • HLA-DR5 Antigen / metabolism
  • Histocompatibility Antigens Class II / biosynthesis
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / metabolism*
  • Humans
  • MART-1 Antigen
  • Melanoma / immunology
  • Melanoma / metabolism
  • Neoplasm Proteins / immunology
  • Neoplasm Proteins / metabolism*
  • Peptide Mapping

Substances

  • Antigens, Neoplasm
  • Epitopes, T-Lymphocyte
  • HLA-DR Antigens
  • HLA-DR Serological Subtypes
  • HLA-DR11 antigen
  • HLA-DR5 Antigen
  • Histocompatibility Antigens Class II
  • MART-1 Antigen
  • MLANA protein, human
  • Neoplasm Proteins