Stevens S Y, Glick G D
Department of Chemistry, University of Michigan, Ann Arbor 48109-1055, USA.
Biochemistry. 1999 Jan 12;38(2):560-8. doi: 10.1021/bi981899o.
Anti-DNA autoantibodies are a serological hallmark of the autoimmune disorder systemic lupus erythematosus. In a process involving antigen recognition, these antibodies are also believed to mediate the kidney inflammation that results in much of the morbidity and mortality associated with lupus. However, the nature of specific DNA antigens recognized by anti-DNA and the way in which anti-DNA interact with these molecules remains poorly understood. As a first step in defining the molecular basis of anti-DNA interactions, binding site selection experiments were conducted using three clonally related murine monoclonal anti-ssDNA autoantibodies previously isolated from a lupus prone MRL-lpr mouse (Swanson, P. C., Ackroyd, P. C., and Glick, G. D. (1996) Biochemistry 35, 1624-1633). Studying the interaction of these autoantibodies with the selected sequences (and variants) through affinity measurements and footprinting experiments provides evidence for sequence-specific binding of ssDNA. However, despite the similarity in amino acid sequence between the three mAbs, only mAb 11F8 appears to possess sequence specificity. The salient features of the interaction between 11F8 and its selected sequence (e.g., limited dependence of ionic strength upon binding, cross-reactivity, and conformational complementarity) are best described by combining the paradigms invoked to explain protein.nucleic acid and antibody.antigen recognition.
抗DNA自身抗体是自身免疫性疾病系统性红斑狼疮的血清学标志。在一个涉及抗原识别的过程中，这些抗体也被认为介导了导致狼疮相关的许多发病率和死亡率的肾脏炎症。然而，抗DNA识别的特定DNA抗原的性质以及抗DNA与这些分子相互作用的方式仍知之甚少。作为确定抗DNA相互作用分子基础的第一步，使用先前从易患狼疮的MRL-lpr小鼠中分离出的三种克隆相关的鼠单克隆抗ssDNA自身抗体进行了结合位点选择实验（Swanson, P. C., Ackroyd, P. C., and Glick, G. D. (1996) Biochemistry 35, 1624 - 1633）。通过亲和力测量和足迹实验研究这些自身抗体与所选序列（及其变体）的相互作用，为ssDNA的序列特异性结合提供了证据。然而，尽管这三种单克隆抗体之间氨基酸序列相似，但只有单克隆抗体11F8似乎具有序列特异性。11F与所选序列之间相互作用的显著特征（例如，结合时离子强度的有限依赖性、交叉反应性和构象互补性）最好通过结合用于解释蛋白质 - 核酸和抗体 - 抗原识别的范例来描述。
