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.