Identification of an HLA-DPB1*0501 restricted Melan-A/MART-1 epitope recognized by CD4+ T lymphocytes: prevalence for immunotherapy in Asian populations.
Identification of an HLA-DPB1*0501 restricted Melan-A/MART-1 epitope recognized by CD4+ T lymphocytes: prevalence for immunotherapy in Asian populations.
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CD4+ T淋巴细胞识别的HLA-DPB1*0501限制的Melan-A/Mart-1表位的鉴定：亚洲人群中免疫疗法的患病率。
DOI：
10.1097/cji.0b013e318226bd45
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发表时间：
2011-09
期刊：
影响因子：
--
通讯作者：
Jiao S
中科院分区：
文献类型：
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作者：
Meng Z;Wang Y;Zhang G;Ke Y;Yan Y;Wu L;Huang Q;Zeng G;Wang Y;Ying H;Jiao S
CD 4 + T淋巴细胞在协调有效的抗肿瘤免疫应答中发挥核心作用。大量的努力已经投入到从不同的肿瘤相关抗原中鉴定主要组织相容性复合物II类表位。Melan-A/ MART-1在75%至100%的黑素瘤患者的正常黑素细胞和肿瘤细胞中特异性表达。Melan-A/MART-1被认为是癌症免疫治疗的有吸引力的靶点。在过去，已经鉴定和表征了几种人类白细胞抗原（HLA）II类限制性表位，包括Melan-A/ MART-11-20（HLA-DR 11限制性），Melan-A/MART-125-36（HLA-DQ 6和HLA-DR 3限制性），Melan-A/MART-127-40（HLA-DR 1限制性）、Melan-A/MART-151-73（HLA-DR 4限制性）、Melan-A/ MART-191-110（HLA-DR 52限制性）和Melan-A/MART-1100-111（HLA-DR 1限制性）。由于上述HLA II类等位基因在亚洲人群中的罕见表达，使用这些定义的Melan-A/MART-1肽的免疫疗法可能仅使非常小比例的亚洲黑色素瘤患者受益。在这项研究中，我们建立了几个CD 4 + T细胞克隆体外刺激外周血单核细胞从健康供体的肽池的28至30个氨基酸长的肽跨越整个Melan-A/MART-1蛋白。这些CD 4 + T细胞克隆以HLA-DPB 1 *0501限制性方式识别嵌入Melan-A/ MART-121-50内的肽。最后，我们证明了这个表位是由树突状细胞自然加工和呈递的。HLA-DPB 1 *0501在亚洲人群中表达频率较高（44.9%~ 73.1%）。因此，这种表位可以提供一种新的工具，并可以显着增加可以从癌症免疫治疗中受益的黑色素瘤患者的百分比。
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.