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

Published

Journal Article

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 tRNA(His). 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.

Full Text

Duke Authors

Cited Authors

  • Miller, FW; Waite, KA; Biswas, T; Plotz, PH

Published Date

  • December 1990

Published In

Volume / Issue

  • 87 / 24

Start / End Page

  • 9933 - 9937

PubMed ID

  • 1702223

Pubmed Central ID

  • 1702223

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.87.24.9933

Language

  • eng

Conference Location

  • United States