Autoimmune disease of the ovary induced by a ZP3 peptide from the mouse zona pellucida.
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.
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.
S H
SH
Rhim
S E
SE
Millar
F
F
Robey
A M
AM
Luo
Y H
YH
Lou
T
T
Yule
P
P
Allen
J
J
Dean
K S
KS
Tung
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D004195:Disease Models, Animal; D004527:Egg Proteins; D000939:Epitopes / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D008562:Membrane Glycoproteins; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009869:Oophoritis / Q000139:chemically induced / Q000276:immunology; D010049:Ovarian Diseases / Q000276:immunology*; D006080:Ovarian Follicle / Q000473:pathology; D011956:Receptors, Cell Surface; D015044:Zona Pellucida / Q000737:chemistry / Q000276:immunology*; D000072216:Zona Pellucida Glycoproteins
D000941:Antigens; D004527:Egg Proteins; D000939:Epitopes; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C000606517:ZP3 protein, human; D000072216:Zona Pellucida Glycoproteins; C000606521:Zp3 protein, mouse