An HLA-A24-restricted cytotoxic T lymphocyte epitope of a tumor-associated protein, survivin.

生存素 表位 细胞毒性T细胞 生物 癌症研究 抗原 人类白细胞抗原 分子生物学 癌细胞 癌症免疫疗法 免疫疗法 癌症 体外 免疫学 免疫系统 生物化学 遗传学
作者
Yoshihiko Hirohashi,Toshihiko Torigoe,Akiko Maeda,Yuki Nabeta,Kenjiro Kamiguchi,Takashi Satō,Junichi Yoda,Hideyuki Ikeda,Kouichi Hirata,Noboru Yamanaka,Noriyuki Sato
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期刊:PubMed 卷期号:8 (6): 1731-9 被引量:55
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To date an increasing number of T-cell epitopes derived from various tumor-associated antigens have been reported, and they proved to play significant roles for tumor rejection both in vivo and in vitro. Survivin was originally identified as a member of the inhibitor of apoptosis protein family. Expression of this gene is developmentally regulated. Although survivin is expressed during normal fetal development, the expression is barely detected in terminally differentiated adult tissues except for testis, thymus, and placenta. In contrast, it is abundantly expressed in a wide variety of malignant tissues. We examined the expression of survivin and the two splicing variants survivin-2B and survivin-DeltaEx3 in various cancer cells, immortalized cells, and normal adult tissues. It was demonstrated that two splicing variants were detected in various types of cancer cells as well as survivin, and their expression was more restricted to cancer cells as compared with survivin expression. To identify HLA-A24-restricted T-cell epitopes from survivin and the variant proteins, three peptides were selected from amino acid sequence of these proteins, based on the HLA-A24-binding motif. Peptide binding assay to HLA-A24 revealed that only one peptide designated as survivin-2B80-88 (AYACNTSTL) was capable of binding to HLA-A24. By stimulating peripheral blood lymphocytes with the peptide-pulsed antigen-presenting cells, CTLs were successfully induced in vitro from five of five HLA-A24-positive cancer patients. The CTLs showed significant cytotoxicity against HLA-A24-positive survivin-2B-positive cancer cells. These data suggest that survivin-2B80-88 may be a potent T-cell epitope eliciting CTL response against a splicing variant survivin-2B, which is specifically expressed in many kinds of cancer cells.

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