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

• Published in: Clinical and experimental immunology 1996-09, Vol.105 (3), p.460-467
• Main Authors: 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.
• Format: Article
• Language: English
• Subjects: Antigen-Antibody Reactions; Antigens, Nuclear; autoantibodies; Autoantibodies - blood; Autoantibodies - chemistry; Autoantibodies - physiology; Autoantigens - chemistry; Autoantigens - immunology; Autoantigens - metabolism; Autoimmune Diseases - immunology; Autoimmune Diseases - metabolism; Autoimmunity (experimental aspects and models); Biological and medical sciences; Catalysis; Chemical Phenomena; Chemistry, Physical; DNA - immunology; DNA Helicases; DNA-Activated Protein Kinase; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - immunology; DNA-Binding Proteins - metabolism; DNA‐dependent protein kinase; DNA‐PKcs; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Histones - immunology; Humans; Immune Sera - chemistry; Immunoblotting; Ku antigen; Ku Autoantigen; Nuclear Proteins - chemistry; Nuclear Proteins - immunology; Nuclear Proteins - metabolism; Original; Precipitin Tests; Protein-Serine-Threonine Kinases - chemistry; Protein-Serine-Threonine Kinases - immunology; Protein-Serine-Threonine Kinases - physiology
• ISSN: 0009-9104; 1365-2249
• 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 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 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.