Autoantibodies that stabilize the molecular interaction of Ku antigen with DNA-dependent protein kinase catalytic subunit

被引:28
|
作者
Satoh, M
Ajmani, AK
Stojanov, L
Langdon, JJ
Ogasawara, T
Wang, J
Dooley, MA
Richards, HB
Winfield, JB
Carter, TH
Reeves, WH
机构
[1] UNIV N CAROLINA, DIV RHEUMATOL & IMMUNOL, DEPT MED, CHAPEL HILL, NC 27599 USA
[2] UNIV N CAROLINA, THURSTON ARTHRITIS RES CTR, DEPT IMMUNOL MICROBIOL, CHAPEL HILL, NC 27599 USA
[3] UNIV N CAROLINA, LINEBERGER COMPREHENS CANC CTR, CHAPEL HILL, NC 27599 USA
[4] KEIO UNIV, SCH MED, DEPT MED, TOKYO 160, JAPAN
[5] ST JOHNS UNIV, DEPT BIOL SCI, JAMAICA, NY 11439 USA
来源
CLINICAL AND EXPERIMENTAL IMMUNOLOGY | 1996年 / 105卷 / 03期
关键词
DNA-dependent protein kinase; Ku antigen; DNA-PKcs; autoantibodies;
D O I
10.1046/j.1365-2249.1996.d01-775.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 biochemically 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 strong 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.
引用
收藏
页码:460 / 467
页数:8
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