Autoimmune disease of the ovary induced by a ZP3 peptide from the mouse zona pellucida

S. H. Rhim, S. E. Millar, F. Robey, A. M. Luo, Y. H. Lou, T. Yule, P. Allen, J. Dean, K. S.K. Tung

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Abstract

We describe a novel experimental system in mice for the study of ovarian autoimmune disease, a condition encountered in women with premature ovarian failure. The ovarian autoimmune disease is induced in B6AF1 mice by a 15-amino acid peptide (Cys-Ser-Asn-Ser-Ser-Ser-Ser-Gln-Phe-Gln-Ile-His-Gly-Pro-Arg) from mouse ZP3, the sperm-binding component of the zona pellucida that surrounds growing and mature oocytes. Whereas the peptide induces both T cell and antibody responses, adoptive transfer of CD4+ T cell lines derived from affected animals causes oophoritis without observable antibodies to the zona pellucida peptide. The primacy of the T cell response in the pathogenesis of disease is further substantiated by defining oophoritogenic peptides as small as eight amino acids (Asn-Ser-Ser-Ser-Ser-Gln-Phe-Gln) that do not elicit an antibody response to the full-length ZP3 peptide. The identification of a well characterized peptide as a causative agent of autoimmune oophoritis should facilitate understanding of the pathogenesis of this T cell-mediated autoimmune disease. Because the proteins of the zona pellucida are conserved among mammals (the mouse and human ZP3 proteins are 67% identical), this murine model may lead to better understanding of the pathogenesis of human autoimmune oophoritis.

Original languageEnglish
Pages (from-to)28-35
Number of pages8
JournalJournal of Clinical Investigation
Volume89
Issue number1
DOIs
StatePublished - Jan 1 1992
Externally publishedYes

Keywords

  • Oophoritis
  • Premature ovarian failure
  • T cell-mediated disease
  • ZP3
  • Zona pellucida

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    Rhim, S. H., Millar, S. E., Robey, F., Luo, A. M., Lou, Y. H., Yule, T., Allen, P., Dean, J., & Tung, K. S. K. (1992). Autoimmune disease of the ovary induced by a ZP3 peptide from the mouse zona pellucida. Journal of Clinical Investigation, 89(1), 28-35. https://doi.org/10.1172/JCI115572