权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

HLA-D ANTIGENS IN INSULIN-DEPENDENT DIABETES

胰岛素依赖型糖尿病中的 HLA-D 抗原

基本信息

批准号：
3447574
负责人：
DIMITRI S MONOS
金额：
$ 5.93万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-12-01 至 1991-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3447574
关键词：
B lymphocyte antibody specificity diabetes mellitus genetics gene expression genetic manipulation high performance liquid chromatography histocompatibility antigens human subject immunogenetics insulin dependent diabetes mellitus protein structure transfection

项目摘要

The objectives of this study are 1) to biochemically identify the specific gene products associated with the HLA-D region that contribute to the susceptibility of Insulin Dependent Diabetes (IDD) and 2) to study the expression of the biochemically identified forms, as IDD specific on transfectant cells. This will be accomplished by using cryopreserved cells and sera from a large number of patients that have been collected and typed for HLA class I and II antigens. In addition, a panel of 23B-lymphoid cell lines (B-LCL) derived from 10 families will be utilized. The study will consist of: 1) Characterization of HLA-DR and DO alpha and beta subunits from B-LCL derived from IDD patient carrying the HLA-DR3 and/or DR4 haplotypes by two dimensional polyacrylamide gel electrophoresis (2D-PAGE), high pressure liquid chromatography (HPLC) and restriction fragment analysis of the DNA (RFLP). 2) Identification of combinatorial (hybrid) DQ antigens forming unique Ia determinants generated as a result of the association of the alpha and beta chains from two haplotypes which can function as restriction elements conferring susceptibility to IDD. 3) Identification of alloantibodies reactive with IDD associated antigens in the sera of multiparous mothers of IDD patients. 4) Isolation of the genes coding for the molecular forms of DR or DO that the biochemical studies indicated to be IDD specific and generation of transfectants expressing these genes. Information generated from this study will help to identify molecular forms more frequently seen among IDD patients and indirectly to use them as markers for identifying those at risk. The transfectants generated will provide an excellent system for studying the genetics of the susceptibility to IDD and will also constitute a model for other Ia associated diseases.

本研究的目的是：1）生物化学鉴定与HLA-D区域相关的特定基因产物，导致胰岛素依赖型糖尿病的易感性 (IDD)和2）研究表达的生化鉴定的形式，如IDD特异性转染细胞。这将通过使用冷冻保存的细胞和血清，大量的病人已经被收集和分类， HLA I类和II类抗原。此外，一组23 B淋巴样将使用来自10个家族的细胞系（B-LCL）。的研究将包括：1）HLA-DR和DO的表征来自IDD患者的B-LCL的α和β亚单位携带HLA-DR 3和/或DR 4单倍型，聚丙烯酰胺凝胶电泳（2D-PAGE），高压液相色谱（HPLC）和限制性片段分析 DNA（RFLP） 2)组合（杂交）的鉴定 DQ抗原形成作为结果产生的独特Ia决定簇从两个不同的基因中单倍型可以作为限制性元件，易患碘缺乏病。 3)同种抗体反应性鉴定经产母亲血清中IDD相关抗原 IDD患者。 4)分离编码以下的基因： DR或DO的分子形式，表明是IDD特异性的，并产生转染子表达这些基因。本研究产生的信息将有助于确定分子形式在IDD患者中更常见，间接地将其用作识别风险人群的标记。所产生的转染子将提供一个极好的系统，研究IDD易感性的遗传学，并将构成了其他Ia相关疾病的模型。