Tolerance to a dominant T cell epitope in the acetylcholine receptor molecule induces epitope spread and suppresses murine myasthenia gravis

Bo Wu, Caishu Deng, Elzbieta Goluszko, Premkumar Christadoss

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Myasthenia gravis (MG) is a T cell-dependent, Ab-mediated autoimmune disease. T cells reactive to a dominant peptide α 146-162 of acetylcholine receptor (AChR) α subunit participate in murine MG pathogenesis. To suppress the autoimmune response to AChR, a high dose of α 146-162 peptide in IFA was administered parenterally as a tolerogen, after the development of a primary T cell immune response to AChR. This form of AChR T cell peptide tolerance suppressed the in vitro T cell proliferative response to AChR and its dominant 146-162 and subdominant α182-198 peptides through epitope spread. Administration of α146-162 peptide in IFA after the primary immune response to AChR also significantly suppressed the serum anti-AChR Ab of the lgG2b isotype and clinical incidence of MG in C57BL/6 mice. Furthermore, the production of IFN-γ, IL-2, and IL-10 cytokines by AChR, α146-162, and α182-198 peptide-reactive cells was suppressed by α146-162 peptide tolerance, and the epitope spread observed could be attributed to the reduction in the above cytokine production. Therefore, AChR T cell-dominant peptide tolerance could be adapted in the Ag-specific therapy of MG.

Original languageEnglish (US)
Pages (from-to)3016-3023
Number of pages8
JournalJournal of Immunology
Volume159
Issue number6
StatePublished - 1997

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T-Lymphocyte Epitopes
Myasthenia Gravis
Cholinergic Receptors
Epitopes
Peptides
T-Lymphocytes
Cytokine Receptors
Autoimmunity
Inbred C57BL Mouse
Interleukin-10
Autoimmune Diseases
Interleukin-2
Cytokines
Incidence

ASJC Scopus subject areas

  • Immunology

Cite this

Tolerance to a dominant T cell epitope in the acetylcholine receptor molecule induces epitope spread and suppresses murine myasthenia gravis. / Wu, Bo; Deng, Caishu; Goluszko, Elzbieta; Christadoss, Premkumar.

In: Journal of Immunology, Vol. 159, No. 6, 1997, p. 3016-3023.

Research output: Contribution to journalArticle

Wu, Bo ; Deng, Caishu ; Goluszko, Elzbieta ; Christadoss, Premkumar. / Tolerance to a dominant T cell epitope in the acetylcholine receptor molecule induces epitope spread and suppresses murine myasthenia gravis. In: Journal of Immunology. 1997 ; Vol. 159, No. 6. pp. 3016-3023.
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AU - Deng, Caishu

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AU - Christadoss, Premkumar

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