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A site-specific antibody produced with a novel immunization procedure by induction of tolerance to cross-reacting determinants and its utilization in clinical research.

通过诱导交叉反应决定簇的耐受性，采用新型免疫程序产生的位点特异性抗体及其在临床研究中的应用。

基本信息

批准号：
61870026
负责人：
HAMAOKA Toshiyuki
金额：
$ 19.52万
依托单位：
Division of Oncogenesis,Department of Oncology, Biomedical Research Center, Osaka University Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1988
项目状态：
已结题

项目摘要

In this study, a novel immunization procedure to produce a site-specific antibody to a ligand of clinical significance with low cross-reactivity was developed and utilized. the method involved the induction of B-lymphocyte tolerance to the cross-reacting determinants on molecules of the ligand in question by treatment of animals with the cross-reacting determinant-d-gl conjugate and immunization with the ligand containing the requisite determinants. 1. Cholecystokinin (CCK)-8-specific antibody was successfully induced by using this immunization procedure, and it was found that the antibody detects biologically active CCK itself but not CCK-precursor and CCK-degradates. 2. By using this CCK-8-specific antibody, CCK was found to widely distribute in central nervous system, except primary sensory neurons, including mesencephalic dopamine neurons and in their projection areas. In addition, CCK levels were significantly reduced in temporal, parietal and occipital cortex of brain of eck fist … More ula dogs and dimethylnitrosamine-treated dogs which were prepared as experimental models of hepatic encphalopathy. Phenylalanine and tyrosine were increased in cortex of these animals. Amounts of reduction of CCK, however, did not correlate with those of increment of the aromatic amino acids in cortex of these models. Thus, these results imply that reduced levels of CCK are elicited by the mechanism distinct from that inducing increase of false neurotransmitter. 3. Neurokinin A- and neurokinin B-specific antibodies were firstly developed by using the abovedevised immunization procedure. Radioimmunoassays using these specific antisera allowed us to measure these neurokinins directly. Measurements of immunoreactive neurokinin A and B in different rat brain regions and spinal cord revealed that they are present with various ratios depending on the region. 4. By utilizing the novel immunization procedure, we are trying to establish the following sitespecific antibodies: antibodies which enable us to distinguish A and B allele of human glucose-6-phosphate dehydrogenase, and antibodies which enable us to distinguish the tumor-related change in in sugar moiety of human choriogonadotropin. Less

在本研究中，开发并利用了一种新的免疫程序，以产生具有低交叉反应性的具有临床意义的配体的位点特异性抗体。该方法包括通过用交叉反应决定因子-d-gl偶联物处理动物和免疫含有必要决定因子的配体，诱导b淋巴细胞对所讨论的配体分子上的交叉反应决定因子的耐受性。1. 利用该免疫程序成功诱导出CCK- 8特异性抗体，发现该抗体只能检测到具有生物活性的CCK本身，而不能检测到CCK前体和降解的CCK。2. 通过CCK-8特异性抗体，发现CCK广泛分布于中枢神经系统，除了初级感觉神经元，包括中脑多巴胺神经元及其投射区。此外，在肝性脑病的实验模型中，更多的实验犬和二甲基亚硝胺处理犬的颞叶、顶叶和枕叶皮层的CCK水平显著降低。这些动物的皮层中苯丙氨酸和酪氨酸增加。然而，CCK的减少量与皮层芳香氨基酸的增加量不相关。因此，这些结果表明CCK水平的降低是由不同于诱导假神经递质增加的机制引起的。3. 神经激肽A和神经激肽b特异性抗体首次使用上述设计的免疫程序。使用这些特异性抗血清的放射免疫测定使我们能够直接测量这些神经激肽。免疫反应性神经激肽A和B在大鼠不同脑区和脊髓的测量表明，它们以不同的比例存在于不同的区域。4. 利用新的免疫程序，我们试图建立以下位点特异性抗体：能够区分人葡萄糖-6-磷酸脱氢酶A和B等位基因的抗体，以及能够区分人绒毛膜促性腺激素糖部分肿瘤相关变化的抗体。少