T CELL RECEPTOR, HLA DISPARITY, & SUCCESSFUL PREGNANCY

三分子复合体是免疫反应性的基石 包括人类白细胞抗原分子、多肽抗原和T细胞受体。 从移植的角度来看，人类白细胞抗原不相容是 与移植排斥反应有关的是，人类白细胞抗原不同的胎儿如何逃脱 排斥反应是一个耐人寻味的免疫学悬而未决的问题。地方因素 在母胎交界处可能是怀孕的关键方面 成功。然而，尽管存在局部因素，一些胎儿细胞还是逃逸到 母体循环。妊娠期的显著缓解 类风湿性关节炎表明对母体系统的影响可能是 系统性的。类风湿关节炎是一种自身免疫性疾病， 具有与特定的人类白细胞抗原II类等位基因相关的特征。我们 最近证明了这种自身免疫性疾病的改善 与胎儿-母亲在人类白细胞抗原II类抗原上的差异有关。这个 这些研究(和其他研究)的结果使我们假设 母体T细胞库在妊娠期间经历变化的反应 进入母体循环的胎儿人类白细胞抗原多肽。在第3至3天 产后6个月类风湿性关节炎几乎没有 例外情况。我们建议检验这样一种假设，即重大变化 发生在怀孕期间和之后的母体T细胞库中 送货。我们预计，这些变化将特别明显。 在分娩前后。这就是本文所述研究的目的 关于表征α-β和γ-βT细胞受体用途的建议 在分娩前后、怀孕前、怀孕期间和怀孕后。从胎儿身上 RA妇女的透视妊娠是非常好的。因此，这种自体免疫 疾病提供了一个人体模型，在这个模型中观察到了全身效应 怀孕期间：一个可以从中获得洞察力的模特- 关于一种神秘的自身免疫性疾病，有利于女性和 关于异体胎儿移植蓬勃发展的成功怀孕。

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.