C3d对原癌基因HER-2/neu基因免疫的调节作用

目的：研究C3d对HER-2／neu基因疫苗诱导的免疫应答的调节作用。方法：分别构建含人HER-2／neu胞外区（hECD）的重组质粒TR421．hECD和hECD与C3d的融合质粒TR421-hECD-C3d3、pcDNA3-hECD-C3d3。以质粒基因免疫小鼠，定期收集血清，以ELISA法检测抗HER-2／neu抗体，3H-TdR掺入法检测细胞免疫应答，观察C3d对hECD免疫应答的调节作用，并以C3d对HBV免疫应答的调节作为对照。结果：hECD-C3d3融合质粒诱导的抗HER-2／neu抗体水平显著低于hECD质粒诱导的抗体水平，其诱导的淋巴细胞增殖反应也显著低于hECD质粒免疫组，但C3d能增强HBV基因免疫诱导的免疫应答。结论：C3d负调控HER-2／neu基因免疫诱导的免疫应答。

The regulation on the immune responses against proto-oncogene HER-2/neu following DNA vaccination by C3d molecule

Objective:To investigate whether C3d can regulate the specific immune responses against HER-2/neu induced by directly injection of naked plasmids DNA containing three tandem repeats of C3d and the extracellular domain of HER-2/neu(hECD).Methods:Recombinant plasmids TR421-hECD encoding hECD gene, TR421-hECD-C3d3 and pcDNA3-hECD-C3d3 encoding hECD-C3d3 fusion gene were constructed. Female BALB/c mice were immunized with these recombinant plasmids three times at three weeks interval. The levels of specific IgG in sera collected at the indicated times from each group were determined by ELISA and specific cellular responses were analyzed by 3H-TdR proliferation assay. As a control, the regulation of C3d on the immune responses against by HBV was evaluated.Results:C3d could enhance the immune responses challenged by HBV. However, the specific antibody response against hECD in the groups primed with hECD-C3d3-DNA was significant lower than that in hECD-DNA groups(P<0.05). And the specific lympho-proliferative response in the mice immunized with hECD-C3d3-DNA was also significant lower than that in hECD-DNA group(P<0.05).Conclusion:These results indicate that three tandem repeats of C3d could negatively regulate the immune responses against HER-2/neu induced by gene immunization.