Analysis of autoantibody production and regulation system using monoclonal anti-DNA antibodies

利用体细胞杂交技术，我们建立了14株产生抗DNA抗体的杂交瘤。根据我们所有的数据，与DNA反应的抗体基本上可以分为两类。一种包括仅与ssDNA反应并且对DNA碱基具有有限特异性的抗体。另一种是血清学多态性的抗体，它们可以与多种多核苷酸反应，包括ssDNA，dsDNA和合成RNA.We选择了三个抗ssDNA单克隆抗体特异性聚（dG），并试图进一步阐明使用半抗原抑制试验的核酸抗原决定簇的精确特异性。结果表明，抗ssDNA单克隆抗体识别的是核酸的一级碱基序列，而不是三级结构; poly（dG）特异性杂交瘤抗体对核酸的碱基和糖部分具有特异性; ...更多信息 部分DNA可能对ssDNA表位的形成贡献很小。多特异性抗DNA抗体（anti-ss/dsDNA）可与心磷脂蛋白发生交叉反应，心磷脂蛋白的化学结构与多核苷酸骨架相似。梅毒血清学生物学假阳性试验（BFP-STS）是SLE患者公认的特征，心磷脂是STS中的主要抗原。因此，推测SLE血清中的BFP反应物是由于具有与ssDNA、dsDNA和心磷脂反应能力的抗体。所有这些发现一起导致了这样的建议，即与核酸的磷酸-糖骨架上的共同抗原决定簇反应的抗DNA抗体可以结合到心磷脂，因为在核酸骨架中存在结构相似性，但不同于BFP反应器。少

Using the somatic cell hybridization technique, we have established 14 hybridomas which produces antibodies to DNA. On the basis of all our data, antibdies reacting with DNA can be basically classified into two groups. One includes antibodies which react exclusively with ssDNA and which have a restricted specificity to DNA base. The other includes antibodies which are serologically polymorphic in that they can react with a variety of polynucleotides including ssDNA, dsDNA and synthetic RNA.We selected three anti-ssDNA monoclonal antibodies specific for poly(dG) and attempted to further elucidate the precise specificity of antigenic determinants of nucleic acids using a hapten inhibition assay. We obtained the results that the anti-ssDNA monoclonal antibody recognized the primary base sequences rather than the tertiary structure of nucleic acids, that the poly(dG) specific hybridoma antibodies had specificity restricted to the base and sugar part of nucleic acids and that the phosphate … More part of DNA may contribute little to the epitope formation of ssDNA. Our data also suggest the mnimal antigenic size of ssDNA corresponds to the tetra- or pentanucleotide.We observed that polyspecific anti-DNA antibodies (anti-ss/dsDNA) could cross-react with cardiolipn, the chemical structure of which is similar to that of polynucleotide backbone. A biological false positive serological test for syphilis (BFP-STS) is a well recognized characteristic of patients with SLE and cardiolipin is a major antigen in the STS. Therefore, it iwas assumed that the BFP reactors in SLE sera were due to the antibodies which had the ability to react with ssDNA, dsDNA and cardiolipin. However, hybridoma capable of binding to both DNA and the VDRL antigen were not detectable.All these findings taken together lead the proposal that anti-DNA antibodies which react with common antigenic determinants on the phosphate-sugar backbone of nucleic acid can bind to the cardiolipn, as there is a structural similarity in the nucleic acid backbone, but differ from the BFP reactors. Less