Open AccessAutoantibodies that stabilize the molecular interaction of Ku antigen with DNA‐dependent protein kinase catalytic subunit
Author(s) -
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.
Publication year - 1996
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1046/j.1365-2249.1996.d01-775.x
Subject(s) - autoantibody , dna pkcs , antibody , antigen , protein subunit , autoimmunity , biology , dna , microbiology and biotechnology , immunology , biochemistry , gene
DNA‐dependent protein kinase (DNA‐PK) consists of a DNA binding subunit (Ku autoantigen), and a catalytic subunit (DNA‐PK cs ). 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‐PK cs with Ku and recognized the DNA‐PK cs –Ku complex, but not biochemically purified DNA‐PK cs . Another type recognized purified DNA‐PK cs . Autoantibodies to Ku (p70/p80 heterodimer), ‘stabilizing’ antibodies, and antibodies to DNA‐PK cs comprise a linked autoantibody set, since antibodies recognizing purified DNA‐PK cs 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‐PK cs ) 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‐PK cs –Ku complex due to autoantibody binding could play a role in spreading autoimmunity from Ku to the weakly associated antigen DNA‐PK cs .