Peptide scanning for thyrotropin receptor T-cell epitopes in mice vaccinated with naked DNA

Pavel Pichurin, Lise Schwarz-Lauer, Helen Braley-Mullen, Charmaine Paras, Oxana Pichurina, John C. Morris, Basil Rapoport, Sandra M. McLachlan

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Vaccinating mice with DNA encoding the thyrotropin receptor (TSHR), the major autoantigen in Graves' disease, induces memory T cells that secrete interferon-γ (IFN-γ) in response to TSHR antigen. We used a panel of 29 synthetic TSHR peptides encompassing the ectodomain and three extracellular loops to identify T-cell epitopes after TSHR-DNA vaccination of BALB/c, NOD.H-2h4, and AKR/N mice. These strains were chosen because of their previous use in animal models of thyroid autoimmunity. In initial studies, challenge of splenocytes with TSHR protein induced IFN-γ and tumor necrosis factor-α (TNF-α) production in all three strains of mice. BALB/c mice recognized three peptides, all in the TSHR A subunit. These peptides differed from the four peptides recognized by nonobese diabetic (NOD mice NOD H-2h4). Three of the latter were also in the A subunit. The fourth was within the intervening C peptide region excised on TSHR cleavage into A and B subunits. Because of high and erratic responses in AKR/N mice, their TSHR T-cell epitopes could not be determined. In summary, we report that TSHR DNA vaccination of BALB/c and NOD.H-2h4 mice, with different major histocompatibility complex (MHC) class II genes (I-Ad and I-Ak, respectively), recognize restricted, nonoverlapping TSHR T-cell epitopes, nearly all in the TSHR A subunit.

Original languageEnglish (US)
Pages (from-to)755-764
Number of pages10
JournalThyroid
Volume12
Issue number9
StatePublished - Sep 2002

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Thyrotropin Receptors
T-Lymphocyte Epitopes
Inbred AKR Mouse
Inbred NOD Mouse
Peptides
DNA
Interferons
Vaccination
MHC Class II Genes
C-Peptide
Major Histocompatibility Complex
Autoimmunity
Thyroid Gland
Animal Models
Tumor Necrosis Factor-alpha
T-Lymphocytes
Antigens
Proteins

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)
  • Endocrinology

Cite this

Pichurin, P., Schwarz-Lauer, L., Braley-Mullen, H., Paras, C., Pichurina, O., Morris, J. C., ... McLachlan, S. M. (2002). Peptide scanning for thyrotropin receptor T-cell epitopes in mice vaccinated with naked DNA. Thyroid, 12(9), 755-764.

Peptide scanning for thyrotropin receptor T-cell epitopes in mice vaccinated with naked DNA. / Pichurin, Pavel; Schwarz-Lauer, Lise; Braley-Mullen, Helen; Paras, Charmaine; Pichurina, Oxana; Morris, John C.; Rapoport, Basil; McLachlan, Sandra M.

In: Thyroid, Vol. 12, No. 9, 09.2002, p. 755-764.

Research output: Contribution to journalArticle

Pichurin, P, Schwarz-Lauer, L, Braley-Mullen, H, Paras, C, Pichurina, O, Morris, JC, Rapoport, B & McLachlan, SM 2002, 'Peptide scanning for thyrotropin receptor T-cell epitopes in mice vaccinated with naked DNA', Thyroid, vol. 12, no. 9, pp. 755-764.
Pichurin P, Schwarz-Lauer L, Braley-Mullen H, Paras C, Pichurina O, Morris JC et al. Peptide scanning for thyrotropin receptor T-cell epitopes in mice vaccinated with naked DNA. Thyroid. 2002 Sep;12(9):755-764.
Pichurin, Pavel ; Schwarz-Lauer, Lise ; Braley-Mullen, Helen ; Paras, Charmaine ; Pichurina, Oxana ; Morris, John C. ; Rapoport, Basil ; McLachlan, Sandra M. / Peptide scanning for thyrotropin receptor T-cell epitopes in mice vaccinated with naked DNA. In: Thyroid. 2002 ; Vol. 12, No. 9. pp. 755-764.
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abstract = "Vaccinating mice with DNA encoding the thyrotropin receptor (TSHR), the major autoantigen in Graves' disease, induces memory T cells that secrete interferon-γ (IFN-γ) in response to TSHR antigen. We used a panel of 29 synthetic TSHR peptides encompassing the ectodomain and three extracellular loops to identify T-cell epitopes after TSHR-DNA vaccination of BALB/c, NOD.H-2h4, and AKR/N mice. These strains were chosen because of their previous use in animal models of thyroid autoimmunity. In initial studies, challenge of splenocytes with TSHR protein induced IFN-γ and tumor necrosis factor-α (TNF-α) production in all three strains of mice. BALB/c mice recognized three peptides, all in the TSHR A subunit. These peptides differed from the four peptides recognized by nonobese diabetic (NOD mice NOD H-2h4). Three of the latter were also in the A subunit. The fourth was within the intervening C peptide region excised on TSHR cleavage into A and B subunits. Because of high and erratic responses in AKR/N mice, their TSHR T-cell epitopes could not be determined. In summary, we report that TSHR DNA vaccination of BALB/c and NOD.H-2h4 mice, with different major histocompatibility complex (MHC) class II genes (I-Ad and I-Ak, respectively), recognize restricted, nonoverlapping TSHR T-cell epitopes, nearly all in the TSHR A subunit.",
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