Immunization with a lymphocytic choriomeningitis virus peptide mixed with heat shock protein 70 results in protective antiviral immunity and specific cytotoxic T lymphocytes.

Immunization with a lymphocytic choriomeningitis virus peptide mixed with heat shock protein 70 results in protective antiviral immunity and specific cytotoxic T lymphocytes.
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与热休克蛋白70混合的淋巴细胞绒毛膜炎病毒肽的免疫接种可导致保护性抗病毒药免疫和特异性细胞毒性T淋巴细胞。

DOI:
10.1084/jem.187.5.685
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发表时间:
1998-03-02
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Welsh RM
Welsh RM
中科院分区:
其他
文献类型:
--
作者:
Ciupitu AM;Petersson M;O'Donnell CL;Williams K;Jindal S;Kiessling R;Welsh RM

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从小鼠癌细胞中分离的热休克蛋白(hsp’s)可以通过将与hsp’s结合的肿瘤衍生肽引导至主要组织相容性I类抗原呈递途径来引发保护性免疫和特异性细胞毒性T淋巴细胞(CTL)。在这里,我们已经调查了热休克蛋白70是否可以用于一种新的肽疫苗诱导保护性抗病毒免疫和记忆性CTL。将来自明确定义的淋巴细胞性脉络丛脑膜炎病毒(LCMV)系统的CTL表位与重组热休克蛋白70在体外在优化肽与热休克蛋白70结合的条件下混合。用hsp 70-肽混合物免疫小鼠并用LCMV攻击。与对照小鼠相比,这些小鼠中的病毒滴度降低了10-100倍。用hsp 70-肽混合物免疫导致CTL记忆细胞的发展,所述CTL记忆细胞可以在LCMV感染期间被重新激活,并且在51 Cr-释放测定中可以裂解用相同肽脉冲的细胞,但不能裂解用另一种LCMV肽脉冲的细胞。这些结果表明,热休克蛋白70可以与CTL表位一起使用,以诱导有效的保护性抗病毒免疫和肽特异性CTL的产生。结果还证明了热休克蛋白70作为佐剂和DNA载体的替代物用于将CTL表位递送至抗原呈递细胞的有用性。
Heat shock proteins (hsp's) isolated from murine cancer cells can elicit protective immunity and specific cytotoxic T lymphocytes (CTLs) by channeling tumor-derived peptides bound to hsp's to the major histocompatibility class I antigen presentation pathway. Here we have investigated if hsp70 can be used in a novel peptide vaccine for the induction of protective antiviral immunity and memory CTLs. A CTL epitope from the well-defined lymphocytic choriomeningitis virus (LCMV) system was mixed with recombinant hsp70 in vitro under conditions that optimize peptide binding to hsp70. Mice were immunized with the hsp70–peptide mixture and challenged with LCMV. Virus titers were reduced 10–100-fold in these mice compared to control mice. Immunization with the hsp70–peptide mixture resulted in the development of CTL memory cells that could be reactivated during LCMV infection, and that in a 51Cr-release assay could lyse cells pulsed with the same peptide, but not cells pulsed with another LCMV peptide. These results show that hsp70 can be used with CTL epitopes to induce efficient protective antiviral immunity and the generation of peptide-specific CTLs. The results also demonstrate the usefulness of hsp70 as an alternative to adjuvants and DNA vectors for the delivery of CTL epitopes to antigen-presenting cells.
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