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Evidence that factors other than particular thyrotropin receptor T cell epitopes contribute to the development of hyperthyroidism in murine Graves' disease.

Abstract：

:Immunization with thyrotropin receptor (TSHR)-adenovirus is an effective approach for inducing thyroid stimulating antibodies and Graves' hyperthyroidism in BALB/c mice. In contrast, mice of the same strain vaccinated with TSHR-DNA have low or absent TSHR antibodies and their T cells recognize restricted epitopes on the TSHR. In the present study, we tested the hypothesis that immunization with TSHR-adenovirus induces a wider, or different, spectrum of TSHR T cell epitopes in BALB/c mice. Because TSHR antibody levels rose progressively from one to three TSHR-adenovirus injections, we compared T cell responses from mice immunized once or three times. Mice in the latter group were subdivided into animals that developed hyperthyroidism and those that remained euthyroid. Unexpectedly, splenocytes from mice immunized once, as well as splenocytes from hyperthyroid and euthyroid mice (three injections), all produced interferon-gamma in response to the same three synthetic peptides (amino acid residues 52-71, 67-86 and 157-176). These peptides were also the major epitopes recognized by TSHR-DNA plasmid vaccinated mice. We observed lesser responses to a wide range of additional peptides in mice injected three times with TSHR-adenovirus, but the pattern was more consistent with increased background 'noise' than with spreading from primary epitopes to dominant secondary epitopes. In conclusion, these data suggest that factors other than particular TSHR T cell epitopes (such as adenovirus-induced expression of conformationally intact TSHR protein), contribute to the generation of thyroid stimulating antibodies with consequent hyperthyroidism in TSHR-adenovirus immunized mice.

journal_name

Clin Exp Immunol

journal_title

Clinical and experimental immunology

authors

Pichurin PN,Chen CR,Nagayama Y,Pichurina O,Rapoport B,McLachlan SM

doi

10.1111/j.1365-2249.2004.02399.x

subject

Has Abstract

pub_date

2004-03-01 00:00:00

pages

391-7

issue

eissn

0009-9104

issn

1365-2249

pii

2399

journal_volume

135

pub_type

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Evidence that factors other than particular thyrotropin receptor T cell epitopes contribute to the development of hyperthyroidism in murine Graves' disease.