PMID- 21760531 OWN - NLM STAT- MEDLINE DCOM- 20111228 LR - 20221207 IS - 1537-4513 (Electronic) IS - 1524-9557 (Print) IS - 1524-9557 (Linking) VI - 34 IP - 7 DP - 2011 Sep TI - Identification of an HLA-DPB1*0501 restricted Melan-A/MART-1 epitope recognized by CD4+ T lymphocytes: prevalence for immunotherapy in Asian populations. PG - 525-34 LID - 10.1097/CJI.0b013e318226bd45 [doi] AB - 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. FAU - Meng, Zhaoting AU - Meng Z AD - Department of Medical Oncology, PLA General Hospital Beijing, China. FAU - Wang, Yadong AU - Wang Y FAU - Zhang, Guanzhong AU - Zhang G FAU - Ke, Yuehua AU - Ke Y FAU - Yan, Yanfeng AU - Yan Y FAU - Wu, Liangliang AU - Wu L FAU - Huang, Qianrong AU - Huang Q FAU - Zeng, Gang AU - Zeng G FAU - Wang, Yu AU - Wang Y FAU - Ying, Han AU - Ying H FAU - Jiao, Shunchang AU - Jiao S LA - eng GR - R03 CA128086/CA/NCI NIH HHS/United States GR - R03 CA128086-02/CA/NCI NIH HHS/United States GR - R21 CA137651/CA/NCI NIH HHS/United States GR - R21 CA137651-01A1/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Immunother JT - Journal of immunotherapy (Hagerstown, Md. : 1997) JID - 9706083 RN - 0 (Antigens, Neoplasm) RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (HLA-DP beta-Chains) RN - 0 (HLA-DPB1*05:01 antigen) RN - 0 (MART-1 Antigen) SB - IM MH - Antigens, Neoplasm/immunology MH - Asian People MH - CD4-Positive T-Lymphocytes/*immunology/metabolism MH - Cell Line, Tumor MH - Dendritic Cells/*immunology MH - Enzyme-Linked Immunosorbent Assay MH - Epitopes, T-Lymphocyte/*immunology MH - HLA-DP beta-Chains/*immunology MH - Histocompatibility Testing MH - Humans MH - Immunotherapy MH - MART-1 Antigen/*biosynthesis/*immunology MH - Melanocytes/metabolism MH - Melanoma/immunology/metabolism MH - T-Lymphocytes, Cytotoxic/immunology/metabolism PMC - PMC4426979 MID - NIHMS366353 COIS- All authors have declared there are no conflicts of interest with regards to this study. EDAT- 2011/07/16 06:00 MHDA- 2011/12/29 06:00 PMCR- 2015/05/11 CRDT- 2011/07/16 06:00 PHST- 2011/07/16 06:00 [entrez] PHST- 2011/07/16 06:00 [pubmed] PHST- 2011/12/29 06:00 [medline] PHST- 2015/05/11 00:00 [pmc-release] AID - 10.1097/CJI.0b013e318226bd45 [doi] PST - ppublish SO - J Immunother. 2011 Sep;34(7):525-34. doi: 10.1097/CJI.0b013e318226bd45.