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首页> 外文期刊>Vaccine >Recognition of endogenously synthesized HLA-DR4 restricted HCV epitopes presented by autologous EBV transformed B-lymphoblastoid cell line
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Recognition of endogenously synthesized HLA-DR4 restricted HCV epitopes presented by autologous EBV transformed B-lymphoblastoid cell line

机译：自体EBV转化的B-淋巴母细胞系呈现的内源性合成的HLA-DR4限制性HCV表位的识别

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摘要

Hepatitis C virus (HCV) causes non-A, non-B hepatitis and infects an estimated 170 million people worldwide. The treatment for HCV infection is often unsuccessful with high costs and many side-effects. There is a great need for alternative therapies including preventive and therapeutic vaccination for HCV infection. The experiments in this study were carried out to elucidate whether endogenously expressed antigen can be presented to helper T-cells restricted by class II molecules and to determine whether responses to plasmid-derived antigen resemble those that we have reported for recombinant antigens or synthetic peptides. To address these issues, a multi-epitope minigene was expressed in 293T-cells and Epstein-Barr virus (EBV)-transformed B-lymphoblastoid cells (BLCL). The transfected BLCLs were employed as APCs to stimulate epitope-specific T-cell hybridomas (THC). The results demonstrated that the endogenously expressed minigene antigens could be processed and presented to T-cell hybridomas by HLA matched BLCL. Five out of seven incorporated epitopes were recognized. Blockade of HLA DR could abolish the release of IL-2, which demonstrated that the endogenously expressed minigene antigens were presented by MHC class II molecules. The presentation of endogenously expressed antigens was much more efficient than that of exogenous antigens, at least in the present study. The findings obtained here have important significance for the development of an HCV DNA vaccine.
机译：丙型肝炎病毒（HCV）引起非甲型，非乙型肝炎，估计感染全世界1亿7千万人。 HCV感染的治疗通常不成功，且费用高且有许多副作用。非常需要替代疗法，包括针对HCV感染的预防性和治疗性疫苗接种。进行这项研究中的实验是为了阐明是否可以将内源表达的抗原呈递给受II类分子限制的辅助性T细胞，并确定对质粒衍生抗原的反应是否类似于我们针对重组抗原或合成肽报道的反应。为了解决这些问题，在293T细胞和爱泼斯坦-巴尔病毒（EBV）转化的B淋巴母细胞（BLCL）中表达了一个多表位的小基因。转染的BLCL被用作APC来刺激表位特异性T细胞杂交瘤（THC）。结果表明内源表达的小基因抗原可以被HLA匹配的BLCL处理并呈递给T细胞杂交瘤。在七个结合的表位中有五个被识别。 HLA DR的阻断可以消除​​IL-2的释放，这表明内源表达的小基因抗原是由MHC II类分子呈递的。至少在本研究中，内源表达的抗原的呈递比外源抗原的呈递效率高得多。此处获得的发现对于HCV DNA疫苗的开发具有重要意义。

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