Moleccular analysis of human leukocyto antigens in trophblast derived cells

滋养层衍生细胞中人类白细胞抗原的分子分析

• 批准号: 06671650
• 负责人: KOYAMA Masayasu
• 金额: $ 1.41万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06671650/
• 关键词: Major histocompatibility; HLA-G; Choriocarcimoma; nuclear factor; NF-kappaB; Gel mobility shift assay; trophoblast; 免疫学的妊娠維持機溝; 転写因子

Mammalian conceptus, which is immunologically semi-allogeneic to the mother, can grow and develop in the mother's uterus avoiding rejection by a component maternal immune system during pregnancy. The molecules on the allogencic fetus and chorionic tissue that arc most active in eliciting an antibody response in the mother arc class 1 major histocompatibility complex (MHC) antigens. We employed several trophoblast derived cell lines to clarify the mechanism regulating the expression of HLA class 1 mRNA at transcriptional level. Northern blot hybridization probed classical HLA class I gene (HLA-A) and nonclassical one (HLA-G) could show the heterogeneity of the expression of HLA class 1 genes among trophoblast cell lines. Using trophoblastic cell lines which express classical HLA class 1, we could demonstrate the nuclear protein that binds the promoter region (enhancer-A) and the expression of this nuclear protein was stimulated by the addition of interfcron-g (published in Am.J.Reprod.Immunol.34 : 323-331 1995). Furthermore, the interaction between nuclear protein and enhancer region was inhibited by anti-NF-kB p5O antibody indicating that the NF-KB p5O protein may play an important regulator to express classical HLA class 1 in trophoblast. On the other hand, we could show that the novel nuclear protein distict from NF-kB protein in the trophoblastic cell line, BeWo, recognizes the specific region located at the promoter region of HLA-G gene (data are submitted in academic journal). Characterization of this novel protein are now on going.

哺乳动物孕体，其在免疫学上与母亲半同种异体，可以在母亲的子宫中生长和发育，避免在怀孕期间被组成部分母体免疫系统排斥。同种异体胎儿和绒毛膜组织上的分子在引起母体抗体反应中最活跃，是1类主要组织相容性复合体（MHC）抗原。本研究采用多种滋养层细胞系从转录水平探讨HLA-1类基因表达的调控机制。北方印迹杂交检测经典HLA I类基因（HLA-A）和非经典HLA I类基因（HLA-G），可显示滋养层细胞系间HLA I类基因表达的异质性。使用表达经典HLA 1类的滋养层细胞系，我们可以证明结合启动子区（增强子-A）的核蛋白，并且该核蛋白的表达被加入干扰素-g刺激（发表于Am.J.Reprod.Immunol.34：323-331 1995）。抗NF-κ B p5 O抗体可抑制核蛋白与增强子区的相互作用，提示NF-κ B p5 O蛋白可能是滋养细胞表达经典HLA-1的重要调节因子。另一方面，我们可以证明，在滋养层细胞系BeWo中，与NF-κ B蛋白区分的新的核蛋白识别位于HLA-G基因启动子区的特异性区域（数据提交在学术期刊上）。这种新蛋白质的表征正在进行中。

项目成果

Tomoyuki Kikuchi et al.: "Loss of biological activity of human chorionic gonadotropin(hCG) by the amino acid substitution on the "CMGCC" region of the alpha subnit" Molecular and Cellular Endocrinology. 102. 1-7 (1994)

Tomoyuki Kikuchi 等人：“α 亚基“CMGCC”区域上的氨基酸取代导致人绒毛膜促性腺激素 (hCG) 的生物活性丧失”《分子和细胞内分泌学》。

K.Hashimoto et al.: "Loss of Imprinting in Choriocarcinoma" Nature Genetics. 9. 109-110 (1995)

K.Hashimoto 等人：“绒毛膜癌中的印记丢失”《自然遗传学》。

Tomoyuki Kikuchi et al.: "Loss of biological activity of human chorionic gonadotrop (hCG)by the amino acid substitution “CMGCC"region of α subun" Mol.Cell.Endocrinology. 102. 1-7 (1994)

Tomoyuki Kikuchi 等人：“α 亚基的氨基酸取代“CMGCC”区域导致人绒毛膜促性腺激素 (hCG) 的生物活性丧失”Mol.Cell.Endocrinology. 102. 1-7 (1994)

The recurrent miscarriage immunotherapy trialists group: "World wide collaborative observational study and meta-analysis on allogenic leukicyte immunotherapy for recurrent spontaneous abortion" Am.J.of Reproduct.Immunol.32. 55-72 (1994)

复发性流产免疫治疗试验小组：“针对复发性自然流产的同种异体白细胞免疫治疗的全球合作观察研究和荟萃分析”Am.J.of Reproduct.Immunol.32。

Akinori Wakimoto et al.: "Regulation of classical HLA class 1 genes in human choriocarcinoma cell by nuclear proteins binding to NHC class 1 regulatory elements" American Journal of Reproductive Immunology. 34. 323-331 (1995)

Akinori Wakimoto 等人：“通过与 NHC 1 类调节元件结合的核蛋白调节人绒毛膜癌细胞中的经典 HLA 1 类基因”美国生殖免疫学杂志。