DNA LEVEL STUDY OF ALLOREACTIVE T-CELL CLONE TARGETS

同种反应性 T 细胞克隆靶标的 DNA 水平研究

• 批准号: 3136585
• 负责人: MASSIMO M. TRUCCO
• 金额: $ 16.5万
• 依托单位: CHILDREN'S HOSP PITTSBURGH/UPMC HLTH SYS
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-07-01 至 1994-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3136585
• 关键词: MHC class II antigen; alleles; antileukocyte isoantibody; clone cells; genetic manipulation; histocompatibility; histocompatibility antigens; human tissue; immunosuppressive antileukocyte serum; isoantibody; laboratory mouse; major histocompatibility complex; molecular cloning; monoclonal antibody; synthetic antigens; transfection

Using restriction fragment length polymorphism analysis (RFLP), three allelic DQ-alpha and three allelic DQ-beta patterns associated DQw1 have been recognized. One of these alpha/beta pairs was found to associate with DR1, two with DR2, and a fourth with DRw6. "Complementary" alloreactive T-cell clones were generated that were able to specifically recognize one or the other of the two DR2 associated, DQw1-positive molecules of the stimulator cells. These molecules carry the same alpha chain but a different (allelic) form of beta chain. In the last few months, evidence has also been obtained by nucleotide sequencing that there are as many allelic forms of DQ-alpha and DQ-beta genes as there are different molecular DQ-alpha and DQ-beta (RFLP) patterns, and each alpha/beta gene combination is associated with the same DR allele as its corresponding molecular alpha/beta pattern pair. It would now be certainly interesting to definitively prove that: a) antibodies may recognize determinants present only on the alpha or on the beta chain of the DQ molecule, while T-cells recognize simultaneously alpha and beta determinants. An allelic modification on only one chain is sufficient to completely abrogate the T-cell alloreaction, but may not interfere with the ability of the antibodies to recognize other epitopes or epitopes of the other chain; b) specificities, against which reagents in general cannot be found because of the strong association of certain alpha with certain beta genes, can be artificially generated by co-transfecting alpha and beta genes in anusual associations; c) specific reagents (monoclonal antibodies as well as T-cell clones) can be generated against these "new" specificities. The spontaneous generation of these "new" specificities may rarely take place by transcomplementation in the presence of particular haplotype combinations. This may be the cause of the immunological failure or the immunological auto-aggression which has generally been found present in the majority of HLA associated diseases. The reagents generated against the artificially obtained "new" specificities would be useful for the early recognition of their presence at the surface of the patient cells.

利用限制性片段长度多态分析(RFLP)， 三种等位基因DQ-α和三种等位基因DQ-β模式 已识别关联的DQw1。其中一个是阿尔法/贝塔 发现与DR1相关的对，两个与DR2相关的对，以及一个 第四名是DRIV6。“互补性”同种异体反应性T细胞克隆 生成了能够专门识别其中一个或 两个DR2相关的DQw1阳性分子中的另一个 刺激细胞。这些分子带有相同的阿尔法链 而是一种不同的(等位基因)形式的β链。在过去的几年里 几个月来，通过核苷酸测序也获得了证据 DQ-α和DQ-β的等位基因形式一样多 基因有不同的分子DQ-α和DQ-β (RFLP)模式，每个α/β基因组合是 与与其相应分子相同的DR等位基因相关联 阿尔法/贝塔模式对。现在肯定会很有趣的是 确凿地证明：a)抗体可以识别决定因素 仅存在于DQ的Alpha或Beta链上 分子，而T细胞同时识别α和β 决定因素。只有一条链上的等位基因修饰是 足以完全消除T细胞同种异体反应，但可能 不会干扰抗体识别其他 另一链的一个或多个表位；b)针对 哪些试剂一般找不到，因为强 某些阿尔法基因与某些贝塔基因的关联，可以是 通过将α基因和β基因共转化到 不常见的联系；c)特殊试剂(单抗 以及T细胞克隆)可以针对这些“新的”产生 具体细节。 这些“新的”特性的自发产生可能 很少在...存在的情况下通过互补性作用发生 特定的单倍型组合。这可能是导致 免疫性失败或免疫性自身攻击 普遍存在于大多数人类白细胞抗原中 相关疾病。产生的试剂是针对 人工获得的“新的”特异性将对 早期识别它们出现在患者的表面 细胞。

项目成果

Epidemiology and immunogenetic background of islet cell antibody--positive nondiabetic schoolchildren. Ulm-Frankfurt population study.

胰岛细胞抗体阳性非糖尿病学童的流行病学和免疫遗传学背景。

• DOI: 10.2337/diab.40.11.1435
• 发表时间: 1991
• 期刊: Diabetes
• 影响因子: 7.7
• 作者: Boehm,BO;Manfras,B;Seissler,J;Schöffling,K;Glück,M;Holzberger,G;Seidl,S;Kühnl,P;Trucco,M;Scherbaum,WA
• 通讯作者: Scherbaum,WA

Immunogenetics of insulin-dependent diabetes mellitus in humans.

人类胰岛素依赖性糖尿病的免疫遗传学。

• 发表时间: 1989
• 期刊: Critical reviews in immunology
• 影响因子: 1.3
• 作者: Trucco,M;Dorman,JS
• 通讯作者: Dorman,JS

Worldwide differences in the incidence of type I diabetes are associated with amino acid variation at position 57 of the HLA-DQ beta chain.

• DOI: 10.1073/pnas.87.19.7370
• 发表时间: 1990-10
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: J. Dorman;Ronald E Laporte;R. Stone;M. Trucco

A new HLA-DR2 extended haplotype is involved in insulin-dependent diabetes mellitus susceptibility.

一种新的 HLA-DR2 扩展单倍型与胰岛素依赖性糖尿病易感性有关。

• DOI: 10.1016/0198-8859(91)90021-z
• 发表时间: 1991
• 期刊: Human immunology
• 影响因子: 2.7
• 作者: Carcassi,C;Trucco,G;Trucco,M;Contu,L
• 通讯作者: Contu,L

The X boxes from promoters of HLA class II B genes at different loci do not complete for nuclear protein-specific binding.

来自不同位点的 HLA II B 类基因启动子的 X 盒不完成核蛋白特异性结合。

• DOI: 10.1007/bf00210449
• 发表时间: 1990
• 期刊: Immunogenetics
• 影响因子: 3.2
• 作者: Turco,E;Manfras,BJ;Ge,L;Rudert,WA;Trucco,M
• 通讯作者: Trucco,M