Autoimmunity to RNA polymerase II is focused at the carboxyl terminal domain of the large subunit

Michito Hirakata, Jyotshna Kanungo, Akira Suwa, Yoshihiko Takeda, Joe Craft, John A. Hardin

研究成果: Article査読

5 被引用数 (Scopus)


Objective. Previous studies have demonstrated antibodies to the large (220 kd) polypeptide subunit of RNA polymerase II (Pol II) in sera from certain patients with scleroderma. In the present study, we sought to identify the autoantigenic region on this polypeptide. Methods. A recombinant fusion protein, corresponding to the 52-heptapeptide repeat found in the carboxyl terminal domain (CTD) of the large Pol II subunit, was used to identify 15 patient sero that contained autoantibodies. Synthetic peptides CTD7 (representing a single heptapeptide) and CTD18 (representing 2 1/4 heptapeptide repeats) were used in a competitive inhibition assay to define the specificity of these sero and the importance of the CTD as an autoantigen. Results. All 15 sera immunoprecipitated the Pol II subunit from radiolabeled cell extracts, and 11 of them bound the CTD fusion protein in immunoblots. Immunoprecipitation of Pol II was completely inhibited by CTD18 in 5 sera and partially inhibited in 4 additional sero. Conclusion. These results indicate that the CTD heptapeptide repeat is a focal point for autoimmune responses in scleroderma. It is likely that the repetitive sequence and high content of charged residues of this structure contribute to its role as an autoantigen.

ジャーナルArthritis and Rheumatism
出版ステータスPublished - 1996 11月

ASJC Scopus subject areas

  • 免疫アレルギー学
  • リウマチ学
  • 免疫学
  • 薬理学(医学)


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