Single chain antibody fragments for the selective targeting of antigens to dendritic cells
Single chain antibody fragments for the selective targeting of antigens to dendritic cells
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DOI：
10.1016/j.molimm.2004.09.034
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发表时间：
2005-05-01
影响因子：
3.6
通讯作者：
Britton, WJ
中科院分区：
文献类型：
--
作者：
Demangel, C;Zhou, J;Britton, WJ
为了将抗原（Ags）选择性地靶向树突状细胞（DC），我们从结合小鼠树突状细胞限制性表面分子DEC-205和CD 11 c的两种单克隆抗体NLDC 145和N418衍生单链抗体片段（scFv）。重组六组氨酸标记形式的scFv（scNLDC和scN 418）在杆状病毒表达系统中有效地产生。两种scFv均结合DEC-205（+）朗格汉斯细胞和CD 11 c（+）胎儿皮肤来源的树突状细胞（FSDCs），使其与其亲本抗体结合。与表达scN 418靶向或非靶向抗原的DNA疫苗相比，用编码与scNLDC融合的模型蛋白抗原的DNA疫苗免疫C57 BL/6小鼠刺激了Immoral和细胞区室中的特异性免疫应答。结果显示，通过DEC-205结合scFv靶向DC的抗原导致增强的免疫原性。此外，这项工作表明，与蛋白质抗原融合并作为DNA疫苗递送的scFv可以提供将疫苗分子递送至选定细胞群体的通用手段。(c)2004 Elsevier Ltd.保留所有权利。
In order to target antigens (Ags) selectively to dendritic cells (DC), we derived single chain antibody fragments (scFvs) from NLDC145 and N418, two monoclonal antibodies binding the mouse dendritic cell-restricted Surface molecules DEC-205 and CD11c. Recombinant hexahistidine-tagged forms of the scFvs (scNLDC and scN418) were efficiently produced in a baculovirus expression system. Both scFvs bound DEC-205(+) Langerhans cells and CD11c(+) fetal skin-derived dendritic cells (FSDCs) comparably to their parental antibodies. Immmunization of C57BL/6 mice with a DNA vaccine encoding a model protein antigen fused to scNLDC stimulated specific immune responses in both the Immoral and cellular compartments, in contrast to DNA vaccines expressing scN418-targeted or untargeted antigen. Out- results show that antigen targeting to DCs via a DEC-205 binding scFv leads to enhanced immunogenicity. Further, this work suggests that scFvs fused to protein antigens and delivered as DNA vaccines may provide a generic means for delivering vaccinal molecules to selected cell Populations. (c) 2004 Elsevier Ltd. All rights reserved.