ANTIBODY MODEL FOR RECOGNITION OF DNA HELICAL DIVERSITY

描述：（改编自研究者摘要）长期目标是 了解对核酸的免疫反应，特别是核酸的起源和 抗DNA自身抗体的性质，这与自身免疫性 系统性红斑狼疮（SLE） 该项目旨在确定 抗体与各种核酸结合所需的结构 构象，以确定狼疮自身抗体是否使用相同的V基因 片段作为外源核酸抗原的抗体，并了解如何 抗DNA反应与B细胞的正常发育有关 保留曲目。 所提出的实验将测试VH或VH的自身反应性。 VH-替代物L链复合物，因为这种自身反应性可能是一种 正选择因子在B细胞库发育中的作用。 下一阶段的具体目标是： 1)继续分析VH和VL结构域的DNA结合作用， 抗DNA抗体中的特定氨基酸或结构基序， 包括通过用Z-DNA、聚（dC）-甲基化 BSA，Cro阻遏蛋白与含有Cro阻遏蛋白的质粒DNA的复合物， 阻遏物靶序列，来自狼疮小鼠的自身抗体（NZB/NZW和 MRL/lpr）和对照免疫诱导的针对无关外源性抗体的抗体 蛋白抗原 2)为了确定来自人的cDNA文库中的VH结构域与来自人的cDNA文库中的VH结构域的频率， 新生小鼠脾脏与DNA和其它自身抗原结合。 3)为了确定VH和替代L链之间的缔合是否 在一些实施方案中，这些组分增强或阻碍DNA结合VH链的自身反应性。 4)为了测试VH区基因重排是否用于 免疫诱导的针对核酸的抗体来源于前体 结合DNA的基因片段VH结构域。

DESCRIPTION: (Adapted from Investigator's abstract) The long term goal is to understand immune responses to nucleic acids, especially the origins and nature of anti-DNA autoantibodies, which are associated with the autoimmune disease systemic lupus erythematosus (SLE). This project aims to identify structures required for antibody binding to various nucleic acid conformations, to determine whether lupus autoantibodies use the same V gene segments as antibodies to exogenous nucleic acid antigens, and to learn how the anti-DNA response is related to normal development of the B cell repertoire. Proposed experiments will test the autoreactivity of VH or VH-surrogate L chain complexes, because such autoreactivity might be a positive selection factor in development of the B cell repertoire. Specific aims for the next period are: 1) to continue analysis of the DNA-binding roles of VH and VL domains and particular amino acids or structural motifs in anti-DNA antibodies, including antibodies induced by immunization with Z-DNA, poly(dC)-methylated BSA, a complex of Cro repressor protein with plasmid DNA containing a Cro repressor target sequence, autoantibodies from lupus mice (NZB/NZW and MRL/lpr) and control immunization-induced antibodies to unrelated exogenous protein antigens. 2) To determine the frequency with which VH domains in a cDNA library from the spleen of a newborn mouse bind to DNA and other autoantigens. 3) To determine whether association between VH and surrogate L chain components enhances or hinders autoreactivty of DNA-binding VH chains. 4) To test whether VH region gene rearrangements use for immunization-induced antibodies to nucleic acids are derived from precursor gene segments VH domains that bind DNA.