肾癌组织中卷曲螺旋结构域蛋白62的HLA-A2表位肽的筛选和鉴定  

Screening and Identification of Peptide of Human Leukocyte Antigen-A2 Epitope of Coiled-coil Domain Containing 62 in the Renal Cell Carcinoma

作　　者：段家晨 乔保平[1] 祁元明 吴亚红 DUAN Jiachen;QIAO Baoping;QI Yuanming;WU Yahong(The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052,China;School of Life Science, Zhengzhou University, Zhengzhou 450001, China)

机构地区：[1]郑州大学第一附属医院,河南郑州450052 [2]郑州大学生命科学学院,河南郑州450001

出　　处：《肿瘤基础与临床》2018年第6期461-464,共4页journal of basic and clinical oncology

基　　金：河南省科技厅基础与前沿技术研究计划基金资助项目(编号:142300410034)

摘　　要：目的筛选和鉴定肾癌组织中癌睾抗原卷曲螺旋结构域蛋白62(CCDC62)的人类白细胞抗原(HLA)-A2的特异性细胞毒性T细胞(CTL)的表位肽,为肾癌的免疫治疗提供实验基础。方法通过NetCTL1.2软件预测CCDC62的HLA-A2限制性表位,对得分>1.0的表位肽进行合成。结合力实验检测候选表位肽与T2A2细胞表面HLA-A2分子的结合强弱,细胞内因子染色检测候选表位肽诱导CTL分泌干扰素-γ(IFN-γ)的能力。比较实验组的表位肽与对照组的差异来判断表位肽的活性。结果表位肽CCDC62-P137和CCDC62-P141有较好的HLA-A2结合力。细胞内因子染色表明表位肽CCDC62-P137相比于对照组能诱导肾癌的CTL分泌更多的IFN-γ。结论表位肽CCDC62-P137有较高的HLA-A2分子亲和力和诱导产生更多IFN-γ的能力,是CCDC62在肾癌组织中的HLA-A2限制性CTL候选表位肽,为肾癌的抗肿瘤多肽治疗提供实验基础。Objective To screen and identify the specific cytotoxic T cell(CTL)epitope peptides of human leukocyte antigen(HLA)-A2 of coiled-coil domain containing 62(CCDC62)in the renal cell carcinoma,and in order to provide the experimental basis for immunotherapy of renal cell carcinoma.Methods The HLA-A2-restricted epitopes of CCDC62 were predicted by NetCTL 1.2 software.The peptides with a score greater than 1.0 were synthesized.Binding experiments of T2A2 cells were performed to test the binding of candidate epitope peptides to HLA-A2 molecules on the surface of T2A2 cells.Intrinsic factor staining was used to examine the ability of candidate epitope peptides to induce CTL to secret IFN-γ.The difference between the antigenic peptide of the experimental group and the control group was compared to judge the activity of the antigen peptide.Results The epitope peptides CCDC62-P137 and CCDC62-P141 have higher HLA-A2 binding scores.Intracellular factor staining showed that the epitope peptide CCDC62-P137 induces more interferon-γIFN-γsecretion from CTL than in the control group in renal cell carcinoma.Conclusion The epitope peptide CCDC62-P137 has a high affinity for HLA-A2 molecules and the ability to induce IFN-γproduction.It is an HLA-A2-restricted CTL candidate epitope peptide of testis antigen CCDC62 in the renal cell carcinoma.This experiment provides the experimental basis for anti-tumor polypeptide therapy of renal cell carcinoma.

关 键 词：肾癌 细胞毒性T细胞 表位肽 人类白细胞抗原 卷曲螺旋结构域蛋白62 

分 类 号：R737.11[医药卫生—肿瘤] R730.23[医药卫生—临床医学]