A novel vaccine strategy to induce mycobacterial antigen-specific Th1 Responses by utilizing the C-terminal domain of heat shock protein 70
A novel vaccine strategy to induce mycobacterial antigen-specific Th1 Responses by utilizing the C-terminal domain of heat shock protein 70
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利用热休克蛋白 70 的 C 端结构域诱导分枝杆菌抗原特异性 Th1 反应的新型疫苗策略
DOI：
10.1111/j.1574-695x.2010.00762.x
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发表时间：
2011
期刊：
影响因子：
--
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et al
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文献类型：
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作者：
K.Chida;et al
热休克蛋白 70 (HSP70) 是高度保守的细胞内伴侣超家族的成员，称为应激蛋白，可以激活先天性和适应性免疫反应。我们评估了编码分枝杆菌 HSP70 和 MPT51（结核分枝杆菌主要分泌蛋白）的融合 DNA 疫苗的效果。与用 MPT51 DNA 免疫的小鼠相比，用全长 HSP70 和 MPT51 融合 DNA 免疫的小鼠的脾细胞对 MPT51 上的 CD4+ 产生更高量的干扰素-γ (IFN-γ)，但对 MPT51 上的 CD8+ T 细胞表位肽不产生反应。此外，由于HSP70包含N端ATP酶结构域和C端肽结合结构域，我们试图鉴定负责其增强作用的结构域。与单独编码 MPT51 的疫苗相比，编码 HSP70 和 MPT51 C 端结构域的融合 DNA 疫苗诱导 CD4+ T 细胞产生更高的 MPT51 特异性 IFN-γ 产量，而具有 N 端结构域的疫苗则不然。通过用融合蛋白进行免疫获得了类似的结果。这些结果表明，编码与分枝杆菌HSP70（尤其是其C末端结构域）融合的嵌合抗原分子的DNA疫苗可以诱导比单独抗原DNA更强的抗原特异性T辅助细胞1型反应。
Heat shock protein 70 (HSP70) is a member of a highly conserved superfamily of intracellular chaperones called stress proteins that can activate innate and adaptive immune responses. We evaluated the effect of a fusion DNA vaccine that encoded mycobacterial HSP70 and MPT51, a major secreted protein ofMycobacterium tuberculosis. Spleen cells from mice immunized with fusion DNA of full-length HSP70 and MPT51 produced a higher amount of interferon-γ (IFN-γ) in response to the CD4+, but not the CD8+ T-cell epitope peptide on MPT51 than those from mice immunized with MPT51 DNA. Furthermore, because HSP70 comprises the N-terminal ATPase domain and the C-terminal peptide-binding domain, we attempted to identify the domain responsible for its enhancing effect. The fusion DNA vaccine that encoded the C-terminal domain of HSP70 and MPT51 induced a higher MPT51-specific IFN-γ production by CD4+ T cells than the vaccine that encoded MPT51 alone, whereas that with the N-terminal domain did not. Similar results were obtained by immunization with the fusion proteins. These results suggest that the DNA vaccine that encodes a chimeric antigen molecule fused with mycobacterial HSP70, especially with its C-terminal domain, can induce a stronger antigen-specific T-helper cell type 1 response than antigen DNA alone.