Molecular mechanism of vaccination effect induced by stress protein-Malaria CS antigen

应激蛋白-疟疾CS抗原诱导疫苗接种效应的分子机制

• 批准号: 11670245
• 负责人: UDONO Heiichiro
• 金额: $ 2.24万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670245/
• 关键词: Plasmodium yoelii; circumsporozoite antigen; hsc70; CTL; vaccine; Hsc70; Plasmodium yoelii; CS蛋白

Immunization with gp96 and hsc70 that bound naturally occurring peptides in vivo or bound synthetic peptides by in vitro reconstitution, have been shown to induce peptide specific CTLs. In addition, mycobacterial hsp70 covalently fused to OVA-derived fragments was shown to generate MHC class I restricted CL responses. In the present study, five different CTL epitopes, including peptides derived from Plasmodium yoelii circumsporozoite protein, tumor antigens, HY antigen and OVA, were genetically fused either to N or C terminus of murine heat shock cognate protein 70 (hsc70), and expressed in E.coli. Peptide specific CTLs were induced by vaccination with all the fusion proteins, indicating that no cognate flanking regions of CTL epitopes are necessary. A root of injection was crucial for CIL induction. CD4^+ T cells were not required for the priming of CD8^+ T cells, and vaccination with bone-marrow derived dendritic cells pulsed with fusion proteins also elicited CL responses. Furthermore, by using deletion mutants of hsc70, the most responsible region of hsc70 to generate CTLs was mapped to hsc70_<280-385>.

使用在体内结合天然存在的肽或通过体外重建结合合成肽的gp96和hsc70进行免疫已被证明可诱导肽特异性CTL。此外，分枝杆菌 hsp70 与 OVA 衍生片段共价融合可产生 MHC I 类限制性 CL 反应。在本研究中，五种不同的 CTL 表位，包括源自约氏疟原虫环子孢子蛋白的肽、肿瘤抗原、HY 抗原和 OVA，通过基因融合到鼠热休克同源蛋白 70 (hsc70) 的 N 或 C 末端，并在大肠杆菌。通过用所有融合蛋白进行疫苗接种来诱导肽特异性CTL，这表明不需要CTL表位的同源侧翼区域。注射根对于 CIL 诱导至关重要。 CD4^+ T 细胞不需要启动 CD8^+ T 细胞，并且用融合蛋白脉冲的骨髓衍生树突状细胞进行疫苗接种也能引发 CL 反应。此外，通过使用hsc70的缺失突变体，hsc70最负责生成CTL的区域被映射到hsc70_<280-385>。

项目成果

Kakeya,H.,Udono,H.et al.: "Heat shock protein 70 (HSP70) as a major target of the antibody response in patients with pulumonary cryptococcosis"Clin.Exp.Immunol.. 115. 485-490 (1999)

Kakeya, H., Udono, H. 等人：“热休克蛋白 70 (HSP70) 作为肺隐球菌病患者抗体反应的主要靶标”Clin.Exp.Immunol.. 115. 485-490 (1999)

Fujiwara,K.,Udono,H.et al.: "Electrophoretic and serologic characterization of 56 kDa antigen (M56) with autologus serum derived from a chondrosarcoma patient: a shared antigen of immunoresponses in cancer and autoimmune diseases"Electrophoresis. 20. 3335

Fujiwara,K.,Udono,H.等人：“使用来自软骨肉瘤患者的自体血清对 56 kDa 抗原 (M56) 进行电泳和血清学表征：癌症和自身免疫性疾病中免疫反应的共享抗原”电泳。

Ishii,T.,Udono,H.et.al.: "Isolation of MHC class I restricted tumorantigen peptide and its precursors associated with heat shock proteins-hsp70,hsp90 and gp96"J.Immunol.. 162. 1303-1309 (1999)

Ishii,T.,Udono,H.et.al.：“MHC I 类限制性肿瘤抗原肽及其与热休克蛋白 -hsp70、hsp90 和 gp96 相关的前体的分离”J.Immunol.. 162. 1303-1309 (1999

Kakeya,H. et al.: "Heat shock protein 70 (HSP70) as a major target of the antibody response in patients with pulumonary cryptococcosis."Clin.Exp.Immunol.. 115. 485-490 (1999)

挂谷，H.

Fujiwara,K. et al.: "Electrophoretic and serologic characterization of 56kDa antigen (M56) with autologus serum derived from a chondrosarcoma patient"Electrophoresis. 20. 3335-3342 (1999)

藤原，K.