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Enhanced iodination of thyroglobulin facilitates processing and presentation of a cryptic pathogenic peptide

Academic Article
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Overview

authors

  • Dai, Yang D.
  • Rao, V. P.
  • Carayanniotis, G.

publication date

  • June 2002

journal

  • Journal of Immunology  Journal

abstract

  • Increased iodine intake has been associated with the development of experimental autoimmune thyroiditis (EAT), but the biological basis for this association remains poorly understood. One hypothesis has been that enhanced incorporation of iodine in thyroglobulin (Tg) promotes the generation of pathogenic T cell determinants. In this study we sought to test this by using the pathogenic nondominant A(s)-binding Tg peptides p2495 and p2694 as model Ags. SJL mice challenged with highly iodinated Tg (I-Tg) developed EAT of higher severity than Tg-primed controls, and lymph node cells (LNC) from I-Tg-primed hosts showed a higher proliferation in response to I-Tg in vitro than Tg-primed LNC reacting to Tg. Interestingly, I-Tg-primed LNC proliferated strongly in vitro against p2495, but not p2694, indicating efficient and selective priming with p2495 following processing of I-Tg in vivo. Tg-primed LNC did not respond to either peptide. Similarly, the p2495-specific, IL-2-secreting T cell hybridoma clone 5E8 was activated when I-Tg-pulsed, but not Tg-pulsed, splenocytes were used as APC, whereas the p2694-specific T cell hybridoma clone 6E10 remained unresponsive to splenic APC pulsed with Tg or I-Tg. The selective in vitro generation of p2495 was observed in macrophages or dendritic cells, but not in B cells, suggesting differential processing of I-Tg among various APC. These data demonstrate that enhanced iodination of Tg facilitates the selective processing and presentation of a cryptic pathogenic peptide in vivo or in vitro and suggest a mechanism that can at least in part account for the association of high iodine intake and the development of EAT.

subject areas

  • Amino Acid Sequence
  • Animals
  • Antigen Presentation
  • Dendritic Cells
  • Female
  • Iodine
  • Macrophages
  • Mice
  • Molecular Sequence Data
  • Thyroglobulin
  • Thyroiditis, Autoimmune
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Identity

International Standard Serial Number (ISSN)

  • 0022-1767

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.168.11.5907

PubMed ID

  • 12023396
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Additional Document Info

start page

  • 5907

end page

  • 5911

volume

  • 168

issue

  • 11

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