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

Clin Exp Immunol. 1996 Sep;105(3):460-7. doi: 10.1046/j.1365-2249.1996.d01-775.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigen-Antibody Reactions
  • Antigens, Nuclear*
  • Autoantibodies / blood
  • Autoantibodies / chemistry
  • Autoantibodies / physiology*
  • Autoantigens / chemistry
  • Autoantigens / immunology*
  • Autoantigens / metabolism*
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / metabolism
  • 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*
  • Histones / immunology
  • Humans
  • Immune Sera / chemistry
  • Immunoblotting
  • Ku Autoantigen
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / immunology*
  • Nuclear Proteins / metabolism*
  • Precipitin Tests
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / immunology*
  • Protein-Serine-Threonine Kinases / physiology*

Substances

  • Antigens, Nuclear
  • Autoantibodies
  • Autoantigens
  • DNA-Binding Proteins
  • Histones
  • Immune Sera
  • Nuclear Proteins
  • DNA
  • DNA-Activated Protein Kinase
  • PRKDC protein, human
  • Protein-Serine-Threonine Kinases
  • DNA Helicases
  • XRCC5 protein, human
  • Xrcc6 protein, human
  • Ku Autoantigen