Hu Fang, Dong Shao-zhong, Liu Long-ding, He Shao-qing, Zhao Shu-dong, Li Qi-han
Department of Immunology, Institute of Medical Biology, CAMS, PUMC, Kunming 650118, China.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2002 Apr;24(2):144-8.
To study the relationship between the structure and functional activity of hTNF alpha.
Four hTNF alpha mutants were constructed, different binding structures and gene responses related with these mutants were studied by the methods of immunoprecipitation and mRNA differential display.
The specific activities and LD50 of the different hTNF alpha mutants indicated their different bioactivities. It was shown that the hTNF alpha mutants had the relative binding affinities to the wild types. The mRNA differential display assay proved that the hTNF alpha mutants stimulated different gene responses.
These results suggest that the specific anti-tumor activities of hTNF alpha mutants are accomplished by inducing different or same gene response at different quantities after its binding to specific receptor.
研究人肿瘤坏死因子α(hTNFα)的结构与功能活性之间的关系。
构建了4种hTNFα突变体,采用免疫沉淀和mRNA差异显示方法研究了与这些突变体相关的不同结合结构和基因反应。
不同hTNFα突变体的比活性和半数致死量(LD50)表明它们具有不同的生物活性。结果显示,hTNFα突变体与野生型具有相对结合亲和力。mRNA差异显示分析证明,hTNFα突变体刺激了不同的基因反应。
这些结果表明,hTNFα突变体的特异性抗肿瘤活性是通过其与特异性受体结合后以不同数量诱导不同或相同的基因反应来实现的。