DOI Seite / Zitierlink:
https://doi.org/10.11588/diglit.48120#0126
108
Molecular and Cell Biology of Autoantibodies and Autoimmunity
epitopes by the cross-reactive antibodies to the UlsnRNP A protein. Thereafter,
the whole molecule could become immunogenic to the host and the other parts
of the protein would then be recognized. The reacting pattern by patients’ sera
to the SS-B/La protein also suggests this possibility. From these studies, it is
postulated that there exist epitope progression phenomena in the autoantibody
production.
Association of Autoantigenic Epitope and Catalytic Site on Poly
(ADP-Ribose) Polymerase
H. Yamanaka1, E.H. Willis2, and D. A. Carson2
1 Institute of Rheumatology, Tokyo Women’s Medical College, NS bldg.,
2-4-1 Nishi-shinjuku, Shinjuku-ku, Tokyo 163, Japan
2 Research Institute of Scripps Clinic, 10666 North Torrey Pines Road, La Jolla,
CA 92037, USA
Poly(ADP-ribose) polymerase is an eukaryotic DNA-binding enzyme, and
transfers the ADP-ribose moiety of NAD to nuclear proteins. This nuclear en-
zyme is strongly activated by DNA with single- or double stand breaks, and has
been postulated to play important roles on DNA repair and DNA replication. We
have identified human autoantibodies to poly(ADP-ribose) polymerase in the sera
of seven rheumatic patients. No other autoantibodies were detected in these pa-
tients sera. The specificity of the autoantibodies to poly(ADP-ribose) polymerase
was established by a) immunoprecipitation and b) immunoprecipitation of en-
zyme activity of poly(ADP-ribose) polymerase.
Nuclear proteins are common targets of autoimmune responses in patients
with systemic rheumatic diseases. However, it is still unclear how abnormal im-
mune regulation leads to the repeated production of autoantibodies against such
a highly selected group of self-components. Although the clinical significance of
autoantibodies to poly(ADP-ribose) polymerase have not been established, the
occurrence of highly specific autoantibodies to this well characterized nuclear en-
zyme is an excellent opportunity to investigate the pathogenesis of the autoan-
tibody production. Since the entire structure of poly(ADP-ribose) polymerase is
known, and cDNA of this protein is isolated, we could examine the epitope
specificity of the human autoantibodies, and their effects on the biological func-
tions of this nuclear enzyme.
Previous experiments have shown that poly(ADP-ribose) polymerase has three
distinctive functional domains, DNA-binding, automodification and NAD-bind-
Molecular and Cell Biology of Autoantibodies and Autoimmunity
epitopes by the cross-reactive antibodies to the UlsnRNP A protein. Thereafter,
the whole molecule could become immunogenic to the host and the other parts
of the protein would then be recognized. The reacting pattern by patients’ sera
to the SS-B/La protein also suggests this possibility. From these studies, it is
postulated that there exist epitope progression phenomena in the autoantibody
production.
Association of Autoantigenic Epitope and Catalytic Site on Poly
(ADP-Ribose) Polymerase
H. Yamanaka1, E.H. Willis2, and D. A. Carson2
1 Institute of Rheumatology, Tokyo Women’s Medical College, NS bldg.,
2-4-1 Nishi-shinjuku, Shinjuku-ku, Tokyo 163, Japan
2 Research Institute of Scripps Clinic, 10666 North Torrey Pines Road, La Jolla,
CA 92037, USA
Poly(ADP-ribose) polymerase is an eukaryotic DNA-binding enzyme, and
transfers the ADP-ribose moiety of NAD to nuclear proteins. This nuclear en-
zyme is strongly activated by DNA with single- or double stand breaks, and has
been postulated to play important roles on DNA repair and DNA replication. We
have identified human autoantibodies to poly(ADP-ribose) polymerase in the sera
of seven rheumatic patients. No other autoantibodies were detected in these pa-
tients sera. The specificity of the autoantibodies to poly(ADP-ribose) polymerase
was established by a) immunoprecipitation and b) immunoprecipitation of en-
zyme activity of poly(ADP-ribose) polymerase.
Nuclear proteins are common targets of autoimmune responses in patients
with systemic rheumatic diseases. However, it is still unclear how abnormal im-
mune regulation leads to the repeated production of autoantibodies against such
a highly selected group of self-components. Although the clinical significance of
autoantibodies to poly(ADP-ribose) polymerase have not been established, the
occurrence of highly specific autoantibodies to this well characterized nuclear en-
zyme is an excellent opportunity to investigate the pathogenesis of the autoan-
tibody production. Since the entire structure of poly(ADP-ribose) polymerase is
known, and cDNA of this protein is isolated, we could examine the epitope
specificity of the human autoantibodies, and their effects on the biological func-
tions of this nuclear enzyme.
Previous experiments have shown that poly(ADP-ribose) polymerase has three
distinctive functional domains, DNA-binding, automodification and NAD-bind-