HLA-G at the Maternal Fetal Interface

来源于主要组织相容性复合体（MHC）Ib类基因HLA-G的糖蛋白首先在 人胎盘，其中它们位于母体蜕膜内和邻近的细胞滋养层（CTB）细胞中。 尽管近二十年的深入研究，这种新基因产物的作用仍然不清楚， 大多数研究指出HLA-G在调节半同种异体妊娠的免疫方面的作用。HLA-G基因 具有许多新的特点：该基因在编码区含有很少的多态性，但在 调节区;至少7种异构体是由来自单个基因的mRNA的选择性剪接产生的; HLAG 具有有限的组织分布，包括在胎盘中的高表达， 在CTB细胞亚群中表达。在这份计划申请中，来自两个机构的三名研究人员提议， 探讨胎盘HLA-G在妊娠中的作用。这三个人，琼亨特博士（堪萨斯大学医学中心， 堪萨斯城，KS），来自同一机构的Margaret Petroff博士和Carole Ober博士（芝加哥大学， 芝加哥，IL）在生殖免疫学方面具有丰富的经验，并将他们的大部分研究集中在MHC上 妊娠期的抗原在项目I中，Hunt将研究亚型特异性表达的机制， 使用新产生的重组可溶性HLA-G糖蛋白的HLA-G亚型特异性功能， 针对这些蛋白质的单克隆抗体。在项目II中，Petroff将研究HLA-G亚型的共表达， B7家族的成员，并将研究使用稳定的免疫细胞功能调节的影响。 表达各种HLA-G/B7蛋白组合的转染细胞。在Project HI中，Ober将追求功能性 使用新开发的等位基因特异性探针的HLA-G基因型方面，并将探讨减少的关系， 生育该计划由两个核心支持。核心A。由亨特领导的行政部门将负责 确保整合和公布实验结果。核心B组织采集和基因分型， 由Ober指导，将收集并向所有研究者提供早期妊娠组织和问题组织 怀孕。该核心还将确定与每个项目相关的基因多态性。调查人员在这 计划完全期望他们的密切和系统的合作将构成一个强大的方法来阐明 HLA-G表达、调节和功能的关键方面，并将最终导致新的和改进的疗法 治疗生育能力受损

Glycoproteins derived from the major histocompatibility complex (MHC) class Ib gene, HLA-G, were first described in human placentas, where they were located in cytotrophoblast (CTB) cells within and adjacent to the maternal decidua. Despite nearly two decades of intensive research, the role(s) of the products of this novel gene remain unclear, although most studies point to a role for HLA-G in regulating immune aspects of semiallogeneic pregnancy. The HLA-G gene has many novel features: the gene contains few polymorphisms in the coding region but multiple polymorphisms in the regulatory regions; at least 7 isoforms are generated by alternative splicing of mRNA derived from a single gene; HLAG has limited tissue distribution that includes high expression in placentas and also demonstrates differential isoform expression in CTB cell subpopulations. In this program application, three investigators from two institutions propose to study the role of placental HLA-G in pregnancy. All three, Dr. Joan Hunt (University of Kansas Medical Center, Kansas City, KS), Dr. Margaret Petroff from the same institution, and Dr. Carole Ober (University of Chicago, Chicago, IL) have extensive experience in reproductive immunology and have focused much of their research on MHC antigens in pregnancy. In Project I, Hunt will investigate mechanisms underlying isoform-specific expression and isoform-specific functions of HLA-G using newly generated recombinant soluble HLA-G glycoproteins and monoclonal antibodies to these proteins. In Project II, Petroff will examine co-expression of HLA-G isoforms and members of the B7 family, and will investigate implications for regulation of immune cell function using stably transfected cells expressing various combinations of HLA-G/B7 proteins. In Project HI, Ober will pursue functional aspects of HLA-G genotypes using newly developed allele-specific probes, and will explore relationships to diminished fertility. The program is supported by two Cores. Core A. Administration, directed by Hunt, will be responsible for assuring integration and publication of the outcomes of the experiments. Core B Tissue Collection and Genotyping, directed by Ober, will collect and supply all investigators with early gestation tissues and tissues from problem pregnancies. This core will also identify polymorphisms in genes relevant to each project. The investigators in this program fully expect that their close and systematic collaboration will comprise a powerful approach to elucidating critical aspects of HLA-G expression, regulation and function, and will ultimately lead to new and improved therapies for impaired fertility.