AUTOIMMUNE-DISEASE OF THE OVARY INDUCED BY A ZP3-PEPTIDE FROM THE MOUSE ZONA-PELLUCIDA
AUTOIMMUNE-DISEASE OF THE OVARY INDUCED BY A ZP3-PEPTIDE FROM THE MOUSE ZONA-PELLUCIDA
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DOI：
10.1172/jci115572
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发表时间：
1992-01-01
影响因子：
15.9
通讯作者：
TUNG, KSK
中科院分区：
文献类型：
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作者：
RHIM, SH;MILLAR, SE;TUNG, KSK
我们描述了一种在小鼠身上研究卵巢自身免疫性疾病的新实验系统，卵巢自身免疫性疾病是一种在卵巢早衰妇女中遇到的情况。B6AF1小鼠的卵巢自身免疫性疾病是由来自小鼠ZP3的15个氨基酸组成的(Cys-Ser-Asn-Ser-Ser-Ser-Ser-Gln-Phe-Gln-Ile-His-Gly-Pro-Arg)诱导的，ZP3是环绕生长和成熟卵母细胞的透明带的精子结合成分。当这种多肽同时诱导T细胞和抗体反应时，过继转移来自受影响动物的CD4+T细胞株会导致卵巢炎，而不能观察到对透明带多肽的抗体。通过定义小至8个氨基酸(ASN-Ser-Gln-Phe-Gln)而不能引起对全长ZP3肽的抗体反应的卵裂素，进一步证实了T细胞反应在疾病发病机制中的首要地位。确定一种具有良好特性的多肽是自身免疫性卵巢炎的病原体，应该有助于理解这种T细胞介导的自身免疫性疾病的发病机制。由于透明带的蛋白质在哺乳动物中是保守的(小鼠和人类的ZP3蛋白有67%相同)，这个小鼠模型可能有助于更好地理解人类自身免疫性卵巢炎的发病机制。
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.