Identification of HLA class I dependent immunogenic peptides from clonotypic TCRβ expressed in cutaneous T-cell lymphoma
Identification of HLA class I dependent immunogenic peptides from clonotypic TCRβ expressed in cutaneous T-cell lymphoma
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DOI：
10.1002/ijc.22113
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发表时间：
2006-11-15
影响因子：
6.4
通讯作者：
Dippel, Edgar
中科院分区：
文献类型：
--
作者：
Zeng, Jinyang;Mueller-Berghaus, Jan;Dippel, Edgar
克隆型 T 细胞受体 (TCR) 是皮肤 T 细胞淋巴瘤 (CTCL) 特异性免疫治疗的潜在靶抗原。我们通过“反向免疫学”方法从恶性 T 细胞群重排的 TCR β 链中鉴定出 T 细胞表位。针对预测表位生成肽特异性 T 细胞系，并测试其对肿瘤细胞和用编码 TCRV β 链的全长 DNA 转染的细胞的识别能力。通过 IFN-gamma ELISpot 测定评估，源自 HLA-A2 阳性患者的克隆型 TCRV β 的两种肽可以从健康供体和患者的外周血单核细胞中诱导肽特异性 T 细胞。此外，反应性CTL可有效识别自体Sezary肿瘤细胞，以及用表达相应TCRVβ29蛋白的重组质粒转染的HLA-A2阳性293细胞。在 HLA-A3+ 患者中，TCRV β 7-J β 2.7 也获得了类似的结果。总之，我们的实验表明 TCR β 链含有适合作为特异性疫苗接种靶点的表位，这可能是皮肤 T 细胞淋巴瘤患者特异性免疫治疗的一种有前途的方法。 (c) 2006 Wiley-Liss, Inc.
The clonotypic T-cell receptor (TCR) is a potential target antigen for specific immunotherapy of cutaneous T-cell lymphoma (CTCL). We identified T-cell epitopes from the rearranged TCR beta chain of the malignant T-cell population by the "reverse immunology" approach. Peptide-specific T-cell lines were generated against predicted epitopes and tested for the recognition of tumor cells and cells transfected with the full-length DNA coding for TCRV beta chain. Two peptides derived from the clonotypic TCRV beta of a HLA-A2 positive patient could induce peptide-specific T cells from peripheral blood mononuclear cells of healthy donors and the patient as assessed by IFN-gamma ELISpot assay. Furthermore, the reactive CTLs efficiently recognized autologous Sezary tumor cells, as well as HLA-A2 positive 293 cells transfected with recombinant plasmid expressing the corresponding TCRV beta 29 protein. Similar results were obtained in a HLA-A3+ patient for TCRV beta 7-J beta 2.7. In conclusion, our experiments show that the TCR beta chain harbors epitopes suitable as targets for specific vaccination which might be a promising approach for the specific immunotherapy of cutaneous T-cell lymphoma patients. (c) 2006 Wiley-Liss, Inc.