Identification of an HLA-DPB1*0501 Restricted Melan-A/MART-1 Epitope Recognized by CD4+ T Lymphocytes: Prevalence for Immunotherapy in Asian Populations

CD4(+) T lymphocytes play a central role in orchestrating an efficient antitumor immune response. Much effort has been devoted in the identification of major histocompatibility complex class II eptiopes from different tumor-associated antigens. Melan-A/MART-1 is expressed specifically in normal melanocytes and tumor cells of 75% to 100% of melanoma patients. Melan-A/MART-1 is considered as an attractive target for cancer immunotherapy. In the past, several human leukocyte antigen (HLA) class II restricted epitopes have been identified and characterized, including Melan-A/MART-1(1-20) (HLA-DR11 restricted), Melan-A/MART-1(25-36) (HLADQ6 and HLA-DR3 restricted), Melan-A/MART-1(27-40) (HLA-DR1 restricted), Melan-A/MART-1(51-73) (HLA-DR4 restricted), Melan-A/MART-1(91-110) (HLA-DR52 restricted), and Melan-A/MART-1(100-111) (HLA-DR1 restricted). Owing to the infrequent expression of the above HLA class II alleles in Asian populations, immunotherapy using these defined Melan-A/MART-1 peptides could potentially only benefit a very small percentage of Asian melanoma patients. In this study, we established several CD4(+) T-cell clones by in vitro stimulation of peripheral blood mononuclear cells from a healthy donor by a peptide pool of 28 to 30 amino acid long peptides spanning the entire Melan-A/MART-1 protein. These CD4(+) T-cell clones recognized a peptide that is embedded within Melan-A/MART-1(21-50), in a HLA-DPB1*0501 restricted manner. Finally, we demonstrated that this epitope is naturally processed and presented by dendritic cells. HLA-DPB1*0501 is frequently expressed in Asian population (44.9% to 73.1%). Therefore, this epitope could provide a new tool and could significantly increase the percentage of melanoma patients that can benefit from cancer immunotherapy.