Identification of a new HLA-A*0201-restricted CD8+ T cell epitope from hepatocellular carcinoma-associated antigen HCA587
Identification of a new HLA-A*0201-restricted CD8+ T cell epitope from hepatocellular carcinoma-associated antigen HCA587
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DOI：
10.1111/j.1365-2249.2005.02786.x
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发表时间：
2005-05-01
影响因子：
4.6
通讯作者：
Chen, W
中科院分区：
文献类型：
--
作者：
Li, B;Wang, Y;Chen, W
为了开发基于肽的癌症免疫治疗，我们的目的是鉴定肝细胞癌（HCC）相关抗原HCA 587中的特异性HLA-A*0201限制性CTL表位，HCA 587已被鉴定为HCC中高度表达的癌症/睾丸（CT）抗原的成员。我们首先将HLA-A*0201/肽结合算法和T2结合测定的使用与通过用高亲和力肽体外引发从正常供体诱导特异性CD 8（+）T细胞系相结合，然后采用IFN-γ释放和细胞毒性测定，使用负载肽的T2细胞或HCA 587蛋白（+）鉴定特异性HLA-A*0201 CD 8（+）T细胞表位。肝癌细胞系HepG 2。在六个候选合成肽中，两个肽在T2结合测定中显示出更高的结合能力。2号肽，包含氨基酸残基FLAKLNNTV（HCA 587（317-325）），能够在来自两名正常供体和两名HCC患者的人淋巴细胞培养物中激活HCA 587特异性CD 8（+）T细胞应答，这些HCA 587特异性CD 8（+）T细胞识别肽脉冲的T2细胞以及IFN-γ中的HCA 587蛋白（+）HCC细胞系HepG 2。γ释放和细胞毒性测定。结果表明，2号肽是一个新的HLA-A*0201限制性CTL表位，能够诱导HCA 587特异性CTL。我们的数据表明，这种新的HCA 587/HLA-A*0201肽FLAKLNNTV的鉴定可能有助于设计用于治疗HCA 587携带HCC患者的基于肽的免疫疗法。
For the development of peptide-based cancer immunotherapies, we aimed to identify specific HLA-A*0201-restricted CTL epitopes in hepatocellular carcinoma (HCC) associated antigen HCA587, which has been identified as a member of the cancer/testis (CT) antigens highly expressed in HCC. We first combined the use of an HLA-A*0201/peptide binding algorithm and T2 binding assays with the induction of specific CD8(+) T cell lines from normal donors by in vitro priming with high-affinity peptides, then IFN-gamma release and cytotoxicity assays were employed to identify the specific HLA-A*0201 CD8(+) T cell epitope using peptide-loaded T2 cells or the HCA587 protein(+) HCC cell line HepG2. In the six candidate synthesized peptides, two peptides showed higher binding ability in T2 binding assays. No. 2 peptide, encompassing amino acid residues FLAKLNNTV (HCA587(317-325)), was able to activate a HCA587-specific CD8(+) T-cell response in human lymphocyte cultures from two normal donors and two HCC patients, and these HCA587-specific CD8(+) T cells recognized peptide-pulsed T2 cells as well as the HCA587 protein(+) HCC cell line HepG2 in IFN-gamma release and cytotoxicity assays. The results indicate that no. 2 peptide is a new HLA-A*0201-restricted CTL epitope capable of inducing HCA587-specific CTLs. Our data suggest that identification of this new HCA587/HLA-A*0201 peptide FLAKLNNTV may facilitate the design of peptide-based immunotherapies for the treatment of HCA587-bearing HCC patients.