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

Publication ,  Journal Article
Miller, FW; Waite, KA; Biswas, T; Plotz, PH
Published in: Proc Natl Acad Sci U S A
December 1990

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.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

December 1990

Volume

87

Issue

24

Start / End Page

9933 / 9937

Location

United States

Related Subject Headings

  • Muscular Diseases
  • Mice, Inbred BALB C
  • Mice
  • Immunoglobulin G
  • Humans
  • Histidine-tRNA Ligase
  • Epitopes
  • Enzyme-Linked Immunosorbent Assay
  • Chromatography, Affinity
  • Autoimmune Diseases
 

Citation

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Miller, F. W., Waite, K. A., Biswas, T., & Plotz, P. H. (1990). The role of an autoantigen, histidyl-tRNA synthetase, in the induction and maintenance of autoimmunity. Proc Natl Acad Sci U S A, 87(24), 9933–9937. https://doi.org/10.1073/pnas.87.24.9933
Miller, F. W., K. A. Waite, T. Biswas, and P. H. Plotz. “The role of an autoantigen, histidyl-tRNA synthetase, in the induction and maintenance of autoimmunity.Proc Natl Acad Sci U S A 87, no. 24 (December 1990): 9933–37. https://doi.org/10.1073/pnas.87.24.9933.
Miller FW, Waite KA, Biswas T, Plotz PH. The role of an autoantigen, histidyl-tRNA synthetase, in the induction and maintenance of autoimmunity. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9933–7.
Miller, F. W., et al. “The role of an autoantigen, histidyl-tRNA synthetase, in the induction and maintenance of autoimmunity.Proc Natl Acad Sci U S A, vol. 87, no. 24, Dec. 1990, pp. 9933–37. Pubmed, doi:10.1073/pnas.87.24.9933.
Miller FW, Waite KA, Biswas T, Plotz PH. The role of an autoantigen, histidyl-tRNA synthetase, in the induction and maintenance of autoimmunity. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9933–9937.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

December 1990

Volume

87

Issue

24

Start / End Page

9933 / 9937

Location

United States

Related Subject Headings

  • Muscular Diseases
  • Mice, Inbred BALB C
  • Mice
  • Immunoglobulin G
  • Humans
  • Histidine-tRNA Ligase
  • Epitopes
  • Enzyme-Linked Immunosorbent Assay
  • Chromatography, Affinity
  • Autoimmune Diseases