The role of an autoantigen, histidyl-tRNA synthetase, in the induction and maintenance of autoimmunity

Frederick W. Miller, Kathleen A. Waite, Tapas Biswas, Paul H. Plotz

Research output: Contribution to journalArticlepeer-review

122 Scopus citations


Patients with systemic autoimmune diseases make specific autoantibodies that are directed against self structures. According to one view, these autoantibodies arise as a result of an immune response to foreign antigens such as infectious agents that share, by molecular mimicry, common structures with host proteins. An alternative view is that the target autoantigen itself initiates, selects, and sustains autoantibody synthesis. We show here that anti-Jo-1 autoantibodies directed against histidyl-tRNA synthetase in the human autoimmune muscle disease polymyositis undergo, in addition to spectrotype broadening and class switching, the sine qua non of an immune response to the target antigen-affinity maturation to that antigen. We demonstrate further that these autoantibodies, unlike anti-synthetase antibodies induced in mice immunized with heterologous antigen, bind only nonlinear epitopes on the native human synthetase that remain exposed when the enzyme is complexed to tRNAHis. These data suggest that the native target autoantigen itself has played a direct role in selecting and sustaining the autoantibody response and sharply restrict the time and the way in which a molecular mimic might act to provoke autoantibodies.

Original languageEnglish (US)
Pages (from-to)9933-9937
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number24
StatePublished - 1990
Externally publishedYes


  • Affinity maturation
  • Anti-Jo-1 autoantibody
  • Conformational epitopes
  • Polymyositis

ASJC Scopus subject areas

  • Genetics
  • General


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