title: Identification of an HLA-DPB1*0501 restricted Melan-A/MART-1 epitope recognized by CD4+ T lymphocytes: prevalence for immunotherapy in Asian populations.
abstract: 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-11-20 (HLA-DR11 restricted), Melan-A/MART-125-36 (HLA-DQ6 and HLA-DR3 restricted), Melan-A/MART-127-40 (HLA-DR1 restricted), Melan-A/MART-151-73 (HLA-DR4 restricted), Melan-A/MART-191-110 (HLA-DR52 restricted), and Melan-A/MART-1100-111 (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-121-50, 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.
authors.affiliation: Department of Medical Oncology, PLA General Hospital Beijing, China.
authors.forename: Zhaoting
authors.initials: Z
authors.lastname: Meng
authors.forename: Yadong
authors.initials: Y
authors.lastname: Wang
authors.forename: Guanzhong
authors.initials: G
authors.lastname: Zhang
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Ke
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Yan
authors.forename: Liangliang
authors.initials: L
authors.lastname: Wu
authors.forename: Qianrong
authors.initials: Q
authors.lastname: Huang
authors.forename: Gang
authors.initials: G
authors.lastname: Zeng
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Han
authors.initials: H
authors.lastname: Ying
authors.forename: Shunchang
authors.initials: S
authors.lastname: Jiao
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology; D044466:Asian People; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D059868:HLA-DP beta-Chains / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007167:Immunotherapy; D058965:MART-1 Antigen / Q000096:biosynthesis* / Q000276:immunology*; D008544:Melanocytes / Q000378:metabolism; D008545:Melanoma / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D059868:HLA-DP beta-Chains; C538744:HLA-DPB1*05:01 antigen; D058965:MART-1 Antigen