Regulation mechanisms of the development of HLA-linked diseases by the complexes of HLA molecules and peptides.

HLA 分子和肽复合物对 HLA 相关疾病发展的调节机制。

基本信息

批准号：
09470060
负责人：
KATAGIRI Makoto
金额：
$ 8.64万
依托单位：
ASAHIKAWA MEDICAL COLLEGE
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470060/
关键词：
HLA molecules HLA-binding peptides Disease susceptibility Allele-specific binding motif 疾患感受性

项目摘要

The profound polymorphism, one of the unique features of HLA molecules, is linked to (a positive association with) the development of certain diseases. Polymorphic region of HLA molecules interact with the corresponding peptides. The complexes then are presented to and stimulate specific T cells, leading to a variety of consequences. Thus the mode the binding of HLA molecules and peptides may affect the process of the development of HLA linked diseases.The primary concern of this project has been the identification of specific peptides possibly involved in the pathogenesis of the diseases, examining the interaction of those peptides with HLA molecules and T cells, and subsequently controlling the disease process.First we have identified the amino acid sequence of the peptides specifically bound to HLA-DR4 and HLA-DR9/DR53, depicting allele specific amino acid sequences (motif). Those two alleles are relatively common in Japanese and are known to have a linkage to certain diseases.Next … More we have investigated peptides which may be involved in the development of such diseases as birch pollinosis, Vogt-Koyanagi-Harada disease and IDDM. We have also examined the possible tumor antigen of malignant melanoma.Our results are summarized as follows,1.Birch pollinosis has a positive association with HLA-DR9. A 17kDa protein has been identified to be a major T cell activating antigen. The protein held three HLA-DR9 restricted epitopes and they all bore DR9 specific binding motif. In patients who had no HLA-DR9 their T cells recognized the epitope containing HLA-DQI binding motif.2.Harada's disease has a positive association with HLA-DR4. T cells from the patient recognized peptides derived from tyrosinase. The peptides bore HLA-DR4 binding motif.3.I-AィイD1g7ィエD1 has a critical role in the development of insulitis and diabetes in NOD mice, a model of IDDM. Two major peptides from glutamic acid decarboxylase 65(GAD65) have been identified to stimulate T cells from NOD mice. Pretreatment of NOD mice with those peptides prevented the development of insulitis.4.Tyrosinase was examined for the possible tumor antigen of malignant melanoma. T cells from melanoma patients recognized the peptide derived from tyrcosinase in HLA-DR15 restricted manner.Our research will present a clue for better understanding a molecular mechanism of disease process and provide the basis for peptide therapy. Less

深刻的多态性是HLA分子的独特特征之一，与某些疾病的发展（正相关）有关。 HLA分子的多态性区域与相应的肽相互作用。然后将复合物呈现给并刺激特定的T细胞，从而导致各种后果。 HLA分子和肽的结合模式可能会影响HLA连接疾病的发展过程。 The primary concern of this project Has been the identification of specific pepperides possible involved in the pathogenesis of the diseases, examining the interaction of those pepperides with HLA molecules and T cells, and subsequently controlling the disease process.First we have identified the amino acid sequence of the pepperides specifically bound to HLA-DR4 and HLA-DR9/DR53, depicting allele specific amino acid sequences (motif).这两个等位基因在日语中相对常见，并且已知与某些疾病有联系。我们还检查了可能的恶性黑色素瘤的肿瘤抗原。您的结果总结如下，1.Birch授粉与HLA-DR9具有正相关。已确定为17KDA蛋白是一种主要的T细胞激活抗原。该蛋白质持有三个HLA-DR9限制的表位，它们都具有DR9特异性结合基序。在没有HLA-DR9的患者中，其T细胞识别含有HLA-DQI结合基序的表位。2。Harada氏病与HLA-DR4具有正相关。来自患者的T细胞识别从酪氨酸酶衍生的肽。肽基HLA-DR4结合基序。3.i-AII D1G7II D1在IDDM模型NOD小鼠的胰岛炎和糖尿病的发展中具有关键作用。已经确定了来自谷氨酸脱羧酶65（GAD65）的两种主要肽，以刺激NOD小鼠的T细胞。用那些胡椒粉对NOD小鼠进行预处理，以阻止胰岛炎的发展。4。酪氨酸酶是否有恶性黑色素瘤可能的肿瘤抗原。来自黑色素瘤患者的T细胞识别出以HLA-DR15受限方式衍生自霸王龙酶的胡椒。我们的研究将提出一种线索，以更好地理解疾病过程的分子机制，并为肽治疗提供了基础。较少的