HLA-G AND NK RECEPTOR INTERACTIONS IN TROPHOBLAST

滋养层中 HLA-G 和 NK 受体的相互作用

• 批准号: 6138737
• 负责人: JONATHAN E BOYSON
• 金额: $ 3.67万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-12-15 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6138737
• 关键词: MHC class I antigen; antigen receptors; cell line; cytolysis; gene targeting; natural killer cells; pregnancy immunology; receptor binding; trophoblast

The fetus expresses paternally-derived as well as maternally- derived molecules and thus can be considered a semi-allogeneic graft with respect to the mother. In the human placenta, most classical MHC class I molecules are not expressed. However, a nonclassical MHC class I molecule, HLA-G, is highly expressed on fetal cells invading the maternal decidua. Although its function remains unclear, these data suggest that HLA-G plays a role in fetal-maternal interactions. Accumulating data suggest that HLA- G serves to protect the otherwise MHC class I-deficient fetal trophoblasts from lysis by maternal decidual natural killer (NK) cells by binding to inhibitory receptors expressed on these cells. Elucidation of the nature of HLA-G/NK cell interactions will be crucial in determining its importance in gestational disease. Aberrant HLA-G expression may lead to gestational complications such as pre-eclampsia, in which there is poor placentation, or spontaneous abortion. To test the hypothesis that HLA-G protects trophoblasts from NK cell lysis, we will generate HLA deletion mutants of the HLA-G-expressing choriocarcinoma (trophoblast) cell line JEG-3 using gene targeting techniques to knock out MHC class I genes. We will then determine whether these mutants are susceptible to lysis by NK cells. Furthermore, we will construct novel multivalent HLA-G tetramers for use as reagents so that we can systematically identify HLA-G receptors and the cells on which they are expressed.

胎儿会表达来自父亲和母亲的- 因此可以认为是半同种异体的 对母亲的尊重。 在人类胎盘中， 经典的MHC I类分子不表达。 但 非经典的MHC I类分子HLA-G，在人外周血中高度表达。 胎儿细胞侵入母体蜕膜。 虽然其功能 目前尚不清楚，这些数据表明HLA-G在 胎儿和母亲的互动 累积的数据表明，HLA- G可以保护其他MHC I类缺陷的胎儿 母体蜕膜自然杀伤细胞（NK）裂解滋养层细胞 通过与这些细胞上表达的抑制性受体结合， 细胞 HLA-G/NK细胞相互作用性质的阐明 将决定其在妊娠中的重要性 疾病 HLA-G表达异常可能导致妊娠 并发症，如先兆子痫，其中有穷人 胎盘形成或自然流产。 为了检验这一假设 HLA-G保护滋养层细胞免受NK细胞裂解，我们将 产生表达HLA-G的HLA缺失突变体， 使用基因的绒毛膜癌（滋养层）细胞系JEG-3 靶向技术来敲除MHC I类基因。 我们将 然后确定这些突变体是否对裂解敏感， NK细胞。 此外，我们将构建新的多价HLA-G 四聚体用作试剂，这样我们就可以系统地 识别HLA-G受体和它们所处的细胞 表达。