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Enhancing or suppressive effects of antibodies on processing of a pathogenic T cell epitope in thyroglobulin

Academic Article
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Overview

authors

  • Dai, Yang D.
  • Carayanniotis, K. A.
  • Eliades, P.
  • Lymberi, P.
  • Shepherd, P.
  • Kong, Y. C. M.
  • Carayanniotis, G.

publication date

  • 1999

journal

  • Journal of Immunology  Journal

abstract

  • Thyroglobulin (Tg)-specific Abs occur commonly in thyroid disease, but it is not clear to what extent they affect Tg processing and presentation to T cells. Here we show that generation of the nondominant pathogenic Tg epitope (2549-2560), containing thyroxine (T4) at position 2553 (T4(2553)), is augmented by Tg-specific IgG mAbs that facilitate FcR-mediated internalization of Tg. However, other mAbs of the same (IgG1) subclass enhanced Tg uptake by APC but had no effect on the generation of this peptide. Treatment of APC with chloroquine or glutaraldehyde abrogated enhanced generation of T4(2553). The boosting effect was selective, since the enhancing mAbs did not facilitate generation of the neighboring cryptic (2495-2511) peptide, which is also pathogenic in mice. When Tg was simultaneously complexed to a mAb reactive with T4(2553) and to a mixture of boosting mAbs, the presentation of this epitope was totally suppressed. These results suggest that Tg-specific Abs alter Tg processing and may boost or suppress the presentation of nondominant pathogenic determinants during the course of disease.

subject areas

  • Adjuvants, Immunologic
  • Animals
  • Antibodies, Blocking
  • Antibodies, Monoclonal
  • Antigen Presentation
  • Antigen-Antibody Complex
  • Antigen-Presenting Cells
  • Base Sequence
  • Cell Line
  • Epitopes, T-Lymphocyte
  • Immunosuppressive Agents
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred CBA
  • Molecular Sequence Data
  • Peptide Fragments
  • Receptors, Fc
  • Thyroglobulin
  • Thyroid Diseases
  • Thyroxine
  • Tumor Cells, Cultured
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Identity

International Standard Serial Number (ISSN)

  • 0022-1767

PubMed ID

  • 10358139
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Additional Document Info

start page

  • 6987

end page

  • 6992

volume

  • 162

issue

  • 12

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