Identification of a novel HLA-A2-restricted cytotoxic T lymphocyte epitope from cancer-testis antigen PLAC1 in breast cancer
Identification of a novel HLA-A2-restricted cytotoxic T lymphocyte epitope from cancer-testis antigen PLAC1 in breast cancer
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乳腺癌中癌睾丸抗原 PLAC1 中新型 HLA-A2 限制性细胞毒性 T 淋巴细胞表位的鉴定
DOI：
10.1007/s00726-011-0966-3
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发表时间：
2012-06-01
期刊：
影响因子：
3.5
通讯作者：
Gao, Yanfeng
中科院分区：
文献类型：
--
作者：
Liu, Wei;Zhai, Mingxia;Gao, Yanfeng
肿瘤抗原的细胞毒性T淋巴细胞（CTL）表位的鉴定是开发抗肿瘤免疫治疗的肽疫苗的关键。在所有的肿瘤抗原中，肿瘤-睾丸（CT）抗原是研究最广泛和最有前途的靶点。PLAC 1（placenta-specific 1，CT 92）被认为是一种新的肿瘤-睾丸抗原，在多种人类恶性肿瘤中表达，以乳腺癌最为常见。在这项研究中，三个天然肽及其类似物来自PLAC 1的T细胞表位预测程序，包括SYFPEGREII，BIMAS和NetCTL 1.2预测。在T2细胞中的结合亲和力和稳定性分析表明，两个天然肽，p28和p31，及其类似物（p28- 1 Y 9 V，p31- 1 Y2 L）对HLA-A*0201分子具有更强的结合活性。在ELISPOT实验中，这4种多肽诱导的CTL均能释放IFN-γ。这4种多肽在体外诱导HLA-A*02+健康人外周血单个核细胞（PBMC）产生的CTL可杀伤MCF-7乳腺癌细胞（HLA-A*0201+，PLAC 1+）。在HLA-A2.1/Kb转基因小鼠中，p28肽诱导的CTL活性最强。因此，我们的研究结果表明，肽p28（VLCSIDWFM）可以作为一个新的候选表位的肽疫苗的发展对PLAC 1阳性乳腺癌。
Identification of cytotoxic T lymphocyte (CTL) epitopes from tumor antigens is essential for the development of peptide vaccines against tumor immunotherapy. Among all the tumor antigens, the caner-testis (CT) antigens are the most widely studied and promising targets. PLAC1 (placenta-specific 1, CT92) was considered as a novel member of caner-testis antigen, which expressed in a wide range of human malignancies, most frequently in breast cancer. In this study, three native peptides and their analogues derived from PLAC1 were predicted by T cell epitope prediction programs including SYFPEITHI, BIMAS and NetCTL 1.2. Binding affinity and stability assays in T2 cells showed that two native peptides, p28 and p31, and their analogues (p28-1Y9 V, p31-1Y2L) had more potent binding activity towards HLA-A*0201 molecule. In ELISPOT assay, the CTLs induced by these four peptides could release IFN-γ. The CTLs induced by these four peptides from the peripheral blood mononuclear cells (PBMCs) of HLA-A*02+healthy donor could lyse MCF-7 breast cancer cells (HLA-A*0201+, PLAC1+) in vitro. When immunized in HLA-A2.1/Kbtransgenic mice, the peptide p28 could induce the most potent peptide-specific CTLs among these peptides. Therefore, our results indicated that the peptide p28 (VLCSIDWFM) could serve as a novel candidate epitope for the development of peptide vaccines against PLAC1-positive breast cancer.