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Research Article Free access | 10.1172/JCI115572

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, and K S Tung

Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.

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Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.

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Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.

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Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.

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Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.

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Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.

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Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.

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Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.

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Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.

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Published January 1, 1992 - More info

Published in Volume 89, Issue 1 on January 1, 1992
J Clin Invest. 1992;89(1):28–35. https://doi.org/10.1172/JCI115572.
© 1992 The American Society for Clinical Investigation
Published January 1, 1992 - Version history
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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.

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