Identification of a Novel CD8+T Cell Epitope Derived from Cancer-Testis Antigen MAGE-4 in Oesophageal Carcinoma
Identification of a Novel CD8+T Cell Epitope Derived from Cancer-Testis Antigen MAGE-4 in Oesophageal Carcinoma
复制标题
食管癌中源自癌睾丸抗原 MAGE-4 的新型 CD8 T 细胞表位的鉴定
DOI：
10.1111/j.1365-3083.2011.02606.x
复制
发表时间：
2011-12-01
影响因子：
3.7
通讯作者：
Ye, Y.
中科院分区：
文献类型：
--
作者：
Wu, Z. Y.;Gao, Y. F.;Ye, Y.
MAGE-4被认为是一种有吸引力的肿瘤-睾丸(CT)抗原，在食道癌(EC)中高表达。为了确定MAGE-4来源的人类白细胞抗原A2限制性表位，用预测程序对天然多肽及其类似物进行了预测。天然多肽p286(KVLEHVVRV)及其类似物p286-1Y2L和p286-1Y2L9L与人类白细胞抗原A*0201分子具有较强的亲和力和稳定性。P286-1Y2L9L诱导的细胞毒性T淋巴细胞(CTL)可释放干扰素？在ELISPOT试验中。在细胞毒实验中，p286-1Y2L9L具有诱导特异性CTL杀伤健康供者PBMCs和HLAA2.1/KB转基因小鼠肿瘤细胞的能力。我们的结果表明，p286-1Y2L9L多肽可以作为一种新的候选表位用于食道癌多肽疫苗的研制。
MAGE-4 is considered as an attractive cancer-testis (CT) antigen for tumour immunotherapy, and it is overexpressed in oesophageal carcinoma (EC). To identify MAGE-4-derived HLA-A2 restricted epitopes, native peptides and their analogues were predicted with prediction programs. The native peptide, p286 (KVLEHVVRV), and its analogues, p286-1Y2L and p286-1Y2L9L, showed potent binding affinity and stability towards HLA-A*0201 molecule. Cytotoxic T lymphocytes (CTLs) induced by p286-1Y2L9L could release IFN-? in ELISPOT assay. In cytotoxicity assay, p286-1Y2L9L showed the capability to induce specific CTLs which could lyse the target cancer cells from both PBMCs of healthy donors and HLA-A2.1/Kb transgenic mice. Our results indicated that the peptide p286-1Y2L9L could serve as a novel candidate epitope to develop peptide vaccines against oesophageal carcinoma.