Oligodeoxynucleotide modifications determine the magnitude of B cell stimulation by CpG motifs
Oligodeoxynucleotide modifications determine the magnitude of B cell stimulation by CpG motifs
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DOI：
10.1089/oli.1.1996.6.133
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发表时间：
1996-06-01
期刊：
影响因子：
--
通讯作者：
Fisher, E
中科院分区：
文献类型：
--
作者：
Krieg, AM;Matson, S;Fisher, E
我们最近报道了含有CpG二核苷酸的寡脱氧核苷酸（ODN），其5‘侧含有两个嘌呤，3’侧含有两个嘧啶，可诱导B细胞增殖和分化。本研究探讨了ODN主干在决定淋巴细胞刺激程度中的作用。硫代磷酸酯ODN的效力大约比磷酸二酯主干的相同序列高2倍。嵌合ODN中，5‘和3’端被核酸酶抗性核苷酸间键修饰，诱导了不同程度的免疫激活，这取决于修饰，磷酸二硫酸键是迄今为止最有效的，并在纳摩尔浓度下诱导B细胞激活，大约比下一个最有效的修饰所需的低1 log，硫酸磷。甲基硫代磷酸酯末端键比磷酸二酯更有效，而磷酸二酯末端键又比甲基膦酸修饰的ODN更有效。
We have recently reported that oligodeoxynucleotides (ODN) that contain a CpG dinucleotide flanked by two purines on the 5'-side and two pyrimidines on the 3'-side induce potent B cell proliferation and differentiation. The present study investigates the role of the ODN backbone in determining the magnitude of the lymphocyte stimulation. Phosphorothioate ODN were approximately 2 logs more potent than the same sequence with a phosphodiester backbone. Chimeric ODN in which the 5'- and 3'-ends were modified with nuclease-resistant internucleotide linkages induced widely varying degrees of immune activation depending on the modification, Phosphorodithioate linkages were by far the most potent and induced B cell activation at nanomolar concentrations, approximately 1 log lower than required for the next most potent modification, phosphorothioate. Methylphosphorothioate terminal linkages were slightly more potent than phosphodiester, which were in turn slightly more potent than terminal methylphosphonate-modified ODN.