Frequent occurrence of anti-tRNA(His) autoantibodies that recognize a conformational epitope in sera of patients with myositis

Arthritis Rheum. 1998 Aug;41(8):1428-37. doi: 10.1002/1529-0131(199808)41:8<1428::AID-ART12>3.0.CO;2-J.

Abstract

Objective: To investigate the incidence of autoantibodies directed to deproteinized transfer RNA(His) (tRNA(His)) in anti-Jo-1 positive myositis patients and to determine the major B cell epitope.

Methods: One hundred sixty-seven myositis sera were screened by immunoblotting and enzyme-linked immunosorbent assay for the presence of anti-Jo-1 antibody. Autoantibodies directed to deproteinized RNA were detected by immunoprecipitation. Ribonuclease cleavage experiments were performed to determine the tRNA(His)-specific features important for recognition.

Results: Approximately one-third of the anti-Jo-1 positive sera also contained autoantibodies recognizing tRNA(His). This recognition was independent of modified bases, but the presence of stabilizing Mg2+ ions appeared to be essential for efficient immunoprecipitation. Transfer RNA(His)-specific features in the anticodon loop were not protected from ribonuclease cleavage by bound antibodies, while protection of bases located in the D and T loops was observed.

Conclusion: A significant number of anti-Jo-1 positive myositis sera contain anti-tRNA(His) activity. Formation of the major autoepitope on tRNA(His) is strongly dependent on proper folding of this molecule mediated by an interaction between D and T loops which is stabilized by either modified residues or Mg2+ ions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantibodies / immunology*
  • Cross Reactions
  • Epitopes / genetics
  • Epitopes / immunology*
  • Histidine-tRNA Ligase / analysis*
  • Humans
  • Molecular Conformation
  • Myositis / genetics
  • Myositis / immunology*
  • Peptide Fragments / immunology
  • Precipitin Tests
  • RNA / immunology
  • RNA, Transfer, His / genetics*
  • RNA, Transfer, His / immunology*

Substances

  • Autoantibodies
  • Epitopes
  • Peptide Fragments
  • RNA, Transfer, His
  • RNA
  • Histidine-tRNA Ligase