T CELL RECEPTOR, HLA DISPARITY, & SUCCESSFUL PREGNANCY

T 细胞受体、HLA 差异、

• 批准号: 2075651
• 负责人: J. Lee Nelson
• 金额: $ 18.01万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-01 至 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2075651
• 关键词: MHC class II antigen; T cell receptor; T lymphocyte; female; histocompatibility antigens; human pregnant subject; human subject; perinatal; postpartum; pregnancy; pregnancy immunology; rheumatoid arthritis

The trimolecular complex is a cornerstone of immunologic responsiveness and includes an HLA molecule, peptide antigen, and the T cell receptor. From the point of view of transplantation in which HLA incompatibility is associated with graft rejection, how the HLA disparate fetus escapes rejection is an intriguing unsolved question of immunology. Local factors at the maternal-fetal interface are likely to be key aspects of pregnancy success. Despite local factors, however, some fetal cells escape into the maternal circulation. The striking remission during pregnancy of rheumatoid arthritis indicates that effects on the maternal system can be systemic. Rheumatoid arthritis is an autoimmune disorder and is characterized by an association with particular HLA class II alleles. We have recently demonstrated that amelioration of this autoimmune disease is associated with fetal-maternal disparity for HLA class II antigens. The results of these studies (and others) have led us to postulate that the maternal T cell repertoire undergoes changes during pregnancy in response to fetal HLA peptides that enter the maternal circulation. During the 3 to 6 months postpartum rheumatoid arthritis returns virtually without exception. We propose to test the hypothesis that significant changes occur in the maternal T cell repertoire during pregnancy and after delivery. We expect that these changes will be particularly apparent around parturition. It is the purpose of the studies described in this proposal to characterize alpha-beta and gamma-delta T cell receptor usage around parturition, before, during and after pregnancy. From the fetal perspective pregnancies of RA women are excellent. Thus this autoimmune disease affords a human model in which a systemic effect is observed during pregnancy: a model from which insights may be gained bi- directionally about an enigmatic autoimmune disease that favors women and about successful pregnancy in which the fetal allograft thrives.

三分子复合物是免疫反应的基石 并且包括HLA分子、肽抗原和T细胞受体。 从移植的角度来看，HLA不相容性是 与移植排斥有关，HLA不同的胎儿如何逃脱 排斥反应是免疫学上一个有趣的未解决的问题。当地因素 可能是怀孕的关键方面 成功然而，尽管有局部因素，一些胎儿细胞还是逃到了 母体循环怀孕期间的显着缓解 类风湿性关节炎表明，对母体系统的影响， 系统性的风湿性关节炎是一种自身免疫性疾病， 其特征在于与特定的HLA II类等位基因相关。我们 最近已经证明，改善这种自身免疫性疾病， 与母胎HLA II类抗原差异相关。的 这些研究（和其他研究）的结果使我们假设， 母体T细胞库在妊娠期间发生变化， 进入母体循环的胎儿HLA肽。在3至 产后6个月类风湿性关节炎几乎没有返回 例外.我们提出检验假设， 发生在母亲的T细胞库在怀孕期间和之后 交付.我们预计这些变化将特别明显 在分娩的时候这是本文所述研究的目的， 表征α-β和γ-δ T细胞受体使用的提案 分娩前后，怀孕前，怀孕期间和怀孕后。从胎儿 RA妇女的妊娠前景非常好。因此，这种自身免疫性 疾病提供了一个人体模型，其中观察到全身效应 怀孕期间：一个模型，从中可以获得见解， 关于一种神秘的自身免疫性疾病， 移植的胎儿能成功受孕。