Comparison of tumor-specific immunogenicities of stress-induced proteins gp96, hsp90, and hsp70.

Comparison of tumor-specific immunogenicities of stress-induced proteins gp96, hsp90, and hsp70.
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DOI:
10.4049/jimmunol.152.11.5398
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发表时间:
1994-06
影响因子:
4.4
通讯作者:
H. Udono;P. K. Srivastava
H. Udono;P. K. Srivastava
中科院分区:
医学2区
文献类型:
--
作者:
H. Udono;P. K. Srivastava

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96 kDa(Gp96)的应激诱导蛋白(或热休克蛋白(HSPs))此前已被证明可诱导对分离出的肿瘤的特异性免疫。在这份报告中,我们表明,与Meth A来源的gp96相反,来自正常组织的gp96制剂在所测试的任何剂量下都不能诱导对Meth A肉瘤的免疫。此外,鉴于最近的研究表明,其他主要的细胞HSP90和HSP70也可以诱导肿瘤特异性免疫,我们比较了来自Meth A肉瘤的gp96、HSP90和HSP70的相对免疫原性。Gp96和HSP70蛋白具有较高的免疫原性,而HSP90的免疫原性约为gp96或HSP70的10%。HSP90的免疫原性差是由于其缺乏可测量的ATPase活性,这与HSPs将多肽转移到受体分子的能力有关。这是第一项记录来自正常组织的gp96制剂缺乏免疫原性的研究,并比较了同一肿瘤系统中三种主要细胞热休克蛋白的免疫原性。
Stress-induced proteins (or heat shock proteins (HSPs)) of 96 kDa size (gp96) have been shown previously to elicit specific immunity to tumors from which they are isolated. In this report, we show that in contrast to Meth A-derived gp96, gp96 preparations derived from normal tissues did not elicit immunity to Meth A sarcoma at any dose tested. Further, in light of recent studies showing that other major cellular HSPs hsp90 and hsp70 also elicit tumor-specific immunity, we have compared the relative immunogenicities of gp96, hsp90, and hsp70 derived from the Meth A sarcoma. The proteins gp96 and hsp70 were observed to be highly and equally immunogenic, whereas the immunogenicity of hsp90 was approximately 10% of that of gp96 or hsp70. It is suggested that the poor immunogenicity of hsp90 results from its lack of a measurable ATPase activity, which has been implicated in the ability of HSPs to transfer peptide to acceptor molecules. This is the first study that documents the lack of immunogenicity of gp96 preparations derived from normal tissues and compares the immunogenicity of each of the three major cellular HSPs in one tumor system.