Thyrotropin Receptor-DNA Vaccination of Transgenic Mice Expressing HLA-DR3 or HLA-DQ6b

Pavel Pichurin, Chun Rong Chen, Oxana Pichurina, Chella David, Basil Rapoport, Sandra M. McLachlan

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Graves' disease in Caucasians is associated with the major histocompatibility (MHC) antigen HLA-DR3. One approach to studying the role of susceptibility genes involves the use of mice that lack murine MHC and instead express human HLA antigens. Although Graves' disease does not arise spontaneously in animals, thyrotropin receptor (TSHR) antibodies can be induced in mice by vaccination with TSHR-DNA in a plasmid. In the present study, we characterized TSHR antibodies and thyroiditis developing in HLA-DR3 transgenic mice vaccinated with TSHR-DNA. As controls, we used mice transgenic for HLA-DQ6b, an MHC antigen rarely associated with Graves' disease. We observed that approximately 30% of DR3-, but none of DQ6b-transgenic mice, developed TSHR antibodies detectable by enzyme-linked immunosorbent assay (ELISA). The cysteine-rich amino terminal peptide was the dominant linear antibody epitope in DR3 mice, as in other strains vaccinated with TSHR-DNA. Sera from some vaccinated DR3 mice were positive on flow cytometry using intact cells expressing the TSHR, demonstrating recognition of the native TSHR on the cell surface. Although none of the these mice had thyroid stimulating antibodies or were hyperthyroid, a few developed lymphocytic infiltration of the thyroid. These data, together with information for other mouse strains, demonstrate that MHC (human and murine) and non-MHC genes contribute to the outcome of TSHR-DNA vaccination and indicate the potential value of DR3 transgenic mice for dissecting immune responses to the TSHR.

Original languageEnglish (US)
Pages (from-to)911-917
Number of pages7
JournalThyroid
Volume13
Issue number10
StatePublished - Oct 2003

Fingerprint

HLA-DR3 Antigen
Thyrotropin Receptors
Transgenic Mice
Vaccination
Histocompatibility
DNA
Graves Disease
Histocompatibility Antigens
Antibodies
Thyroid-Stimulating Immunoglobulins
Thyroiditis
Hyperthyroidism
HLA Antigens
Genes
Cysteine
Epitopes
Flow Cytometry
Thyroid Gland
Plasmids
Enzyme-Linked Immunosorbent Assay

ASJC Scopus subject areas

  • Endocrinology

Cite this

Pichurin, P., Chen, C. R., Pichurina, O., David, C., Rapoport, B., & McLachlan, S. M. (2003). Thyrotropin Receptor-DNA Vaccination of Transgenic Mice Expressing HLA-DR3 or HLA-DQ6b. Thyroid, 13(10), 911-917.

Thyrotropin Receptor-DNA Vaccination of Transgenic Mice Expressing HLA-DR3 or HLA-DQ6b. / Pichurin, Pavel; Chen, Chun Rong; Pichurina, Oxana; David, Chella; Rapoport, Basil; McLachlan, Sandra M.

In: Thyroid, Vol. 13, No. 10, 10.2003, p. 911-917.

Research output: Contribution to journalArticle

Pichurin, P, Chen, CR, Pichurina, O, David, C, Rapoport, B & McLachlan, SM 2003, 'Thyrotropin Receptor-DNA Vaccination of Transgenic Mice Expressing HLA-DR3 or HLA-DQ6b', Thyroid, vol. 13, no. 10, pp. 911-917.
Pichurin P, Chen CR, Pichurina O, David C, Rapoport B, McLachlan SM. Thyrotropin Receptor-DNA Vaccination of Transgenic Mice Expressing HLA-DR3 or HLA-DQ6b. Thyroid. 2003 Oct;13(10):911-917.
Pichurin, Pavel ; Chen, Chun Rong ; Pichurina, Oxana ; David, Chella ; Rapoport, Basil ; McLachlan, Sandra M. / Thyrotropin Receptor-DNA Vaccination of Transgenic Mice Expressing HLA-DR3 or HLA-DQ6b. In: Thyroid. 2003 ; Vol. 13, No. 10. pp. 911-917.
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