Identification of an immunodominant H-2Db-restricted CTL epitope of human PSA
Identification of an immunodominant H-2Db-restricted CTL epitope of human PSA
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DOI：
10.1002/pros.20221
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发表时间：
2005-06-15
期刊：
影响因子：
2.8
通讯作者：
Pisa, P
中科院分区：
文献类型：
--
作者：
Pavlenko, M;Leder, C;Pisa, P
背景。人前列腺特异性抗原（PSA）在前列腺上皮中选择性表达，是前列腺癌免疫治疗的潜在靶点。据报道，各种基于 PSA 的疫苗可在动物模型中诱导细胞毒性 T 淋巴细胞 (CTL) 反应。在这里，我们介绍了 C57B1/6 小鼠 (H-2(b)) 中 PSA 免疫显性 CTL 表位的鉴定和验证。通过用表达 PSA 的质粒进行免疫来诱导 PSA 特异性 CTL。 CTL 的表位特异性是通过它们对一组 C 末端截短或突变的 PSA 蛋白的反应性以及使用 SYFPEITHI 算法进行生物信息预测来确定的。结果。大多数 PSA 特异性 CTL 针对对应于蛋白质氨基酸残基 65-74 (HCIRNKSVIL) 的单个 H-2D(b) 限制性表位。 CTL 对两种假定的 H-2D(b) 结合肽具有相似的功能亲和力：9 个氨基酸长的 psa65-73 (HCIRNKSVI) 和 10 个氨基酸长的 psa65-74 (HCIRNKSVIL)。 结论。我们证明 psa65-73 肽可用于体外和离体重新激活 PSA 特异性 CTL，并且用该肽组装的 H-2Db 五聚体是监测 DNA 疫苗接种后 PSA 特异性 CTL 反应的有效工具。 (c) 2005 年 Wiley-Liss, Inc.
BACKGROUND. Human prostate specific antigen (PSA) is expressed selectively in prostate epithelium and is a potential target for the immunotherapy against prostate cancer. Various PSA-based vaccines have been reported to induce cytotoxic T lymphocyte (CTL.) responses in animal models. Here, we present the identification and validation of an immunodominant CTL epitope of PSA in C57B1/6 mice (H-2(b)).METHODS. PSA-specific CTLs were induced by immunization with a plasmid expressing PSA. Epitope specificity of the CTLs was determined by their reactivity against a panel of C-terminus truncated or mutated PSA proteins and use of bioinformatical prediction with the SYFPEITHI algorithm.RESULTS. The majority of PSA-specific CTLs were directed against a single H-2D(b) restricted epitope corresponding to the amino acid residues 65-74 (HCIRNKSVIL) of the protein. The CTLs had similar functional avidity against two putative H-2D(b) binding peptides: a 9-aa-long psa65-73 (HCIRNKSVI) and a 10-aa-long psa65-74 (HCIRNKSVIL).CONCLUSIONS. We demonstrate that the psa65-73 peptide can be used for reactivation of PSA-specific CTLs in vitro and ex vivo, and H-2Db pentamers assembled with this peptide are an efficient tool for monitoring of PSA-specific CTL responses after DNA vaccination. (c) 2005 Wiley-Liss, Inc.