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

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.