Krishnan M R, Marion T N
Department of Microbiology and Immunology, University of Tennessee, Memphis 38163.
J Immunol. 1993 Jun 1;150(11):4948-57.
Anti-DNA antibodies have been successfully induced in normal, nonautoimmune mice by immunization with complexes formed with a DNA-binding peptide, Fus1, and native, B form, mammalian DNA. Fus1 is a 27-amino acid peptide from the internal domain of a ubiquitin fusion protein from Trypanosoma cruzi. The structure of this peptide is homologous to the consensus amino acid sequence for a DNA-binding, "zinc finger" motif, and the peptide binds to DNA. A panel of six anti-DNA antibody-producing hybridomas, two IgM and four IgG2a, have been generated from a single BALB/c mouse immunized with Fus1-DNA. The V region structures for both H and L chains of the induced anti-DNA antibodies are highly homologous if not identical to the V region structures of spontaneous anti-DNA antibodies from autoimmune (NZB x NZW)F1 mice. The DNA specificities of the anti-DNA antibodies were also similar to those of autoimmune anti-DNA antibodies. Three of the four induced IgG antibodies bound equally well to native and denatured DNA. These results demonstrate that antibody specific for nDNA can be induced with immunogenic complexes of native DNA. They also demonstrate that monoclonal representatives of the induced anti-DNA antibodies have serologic and structural characteristics similar if not identical to those of spontaneous anti-DNA antibodies from autoimmune mice. The experimental system described here should provide insight not only about the structural basis for autoimmunity to DNA but also the function of anti-DNA antibody in the immunopathology of SLE.
通过用与DNA结合肽Fus1和天然B型哺乳动物DNA形成的复合物免疫正常的非自身免疫小鼠，成功诱导出了抗DNA抗体。Fus1是来自克氏锥虫泛素融合蛋白内部结构域的27个氨基酸的肽。该肽的结构与DNA结合“锌指”基序的共有氨基酸序列同源，并且该肽可与DNA结合。用Fus1-DNA免疫一只BALB/c小鼠，产生了一组六个产生抗DNA抗体的杂交瘤，其中两个为IgM，四个为IgG2a。诱导产生的抗DNA抗体的重链和轻链的V区结构即使与自身免疫性（NZB×NZW）F1小鼠自发产生的抗DNA抗体的V区结构不完全相同，也高度同源。抗DNA抗体的DNA特异性也与自身免疫性抗DNA抗体相似。四个诱导产生的IgG抗体中有三个与天然DNA和变性DNA的结合能力相同。这些结果表明，天然DNA的免疫原性复合物可诱导产生对天然DNA具有特异性的抗体。它们还表明，诱导产生的抗DNA抗体的单克隆代表具有与自身免疫小鼠自发产生的抗DNA抗体相似（如果不是完全相同）的血清学和结构特征。本文所述的实验系统不仅应能深入了解针对DNA自身免疫的结构基础，还能深入了解抗DNA抗体在系统性红斑狼疮免疫病理学中的作用。
