Satoh M, Ajmani A K, Stojanov L, Langdon J J, Ogasawara T, Wang J, Dooley M A, Richards H B, Winfield J B, Carter T H, Reeves W H
Department of Medicine, University of North Carolina, Chapel Hill 27599-7280, USA.
Clin Exp Immunol. 1996 Sep;105(3):460-7. doi: 10.1046/j.1365-2249.1996.d01-775.x.
DNA-dependent protein kinase (DNA-PK) consists of a DNA binding subunit (Ku autoantigen), and a catalytic subunit (DNA-PKcs). In the present study, human autoantibodies that recognize novel antigenic determinants of DNA-PK were identified. One type of autoantibody stabilized the interaction of DNA-PKcs with Ku and recognized the DNA-PKcs -Ku complex, but not bio-chemically purified DNA-PKcs. Another type recognized purified DNA-PKcs. Autoantibodies to Ku (p70/p80 heterodimer), 'stabilizing' antibodies, and antibodies to DNA-PKcs comprise a linked autoantibody set, since antibodies recognizing purified DNA-PKcs were strongly associated with stabilizing antibodies, whereas stabilizing antibodies were strongly associated with anti-Ku. This hierarchical pattern of autoantibodies specific for components of DNA-PK (anti-Ku > stabilizing antibodies > anti-DNA-PKcs) may have implications for the pathogenesis of autoimmunity to DNA-PK and other chromatin particles. The data raise the possibility that altered antigen processing and/or stabilization of the DNA-PKcs-Ku complex due to autoantibody binding could play a role in spreading autoimmunity from Ku to the weakly associated antigen DNA-PKcs.
DNA依赖性蛋白激酶（DNA-PK）由一个DNA结合亚基（Ku自身抗原）和一个催化亚基（DNA-PKcs）组成。在本研究中，鉴定出了识别DNA-PK新抗原决定簇的人自身抗体。一种自身抗体可稳定DNA-PKcs与Ku的相互作用，并识别DNA-PKcs-Ku复合物，但不能识别生化纯化的DNA-PKcs。另一种则识别纯化的DNA-PKcs。针对Ku（p70/p80异二聚体）的自身抗体、“稳定化”抗体以及针对DNA-PKcs的抗体构成了一组相关的自身抗体，因为识别纯化DNA-PKcs的抗体与稳定化抗体高度相关，而稳定化抗体与抗Ku高度相关。这种针对DNA-PK组分的自身抗体的层级模式（抗Ku＞稳定化抗体＞抗DNA-PKcs）可能与针对DNA-PK和其他染色质颗粒的自身免疫发病机制有关。这些数据提出了一种可能性，即由于自身抗体结合导致的DNA-PKcs-Ku复合物抗原加工改变和/或稳定化可能在自身免疫从Ku扩散到弱相关抗原DNA-PKcs中起作用。
