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Analysis of T cell epitopes in the patients with the antiphospholipid syndrome.

抗磷脂综合征患者T细胞表位分析

基本信息

批准号：
09670461
负责人：
TSUTSUMI Akito
金额：
$ 1.02万
依托单位：
HOKKAIDO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
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

项目摘要

I) Efforts were made to establish monoclonal anti-βィイD22ィエD2-GPI and anti-prothrombin antibodies from peripheral blood lymphocytes of patients with antiphospholipid syndrome (APS).ii) A random peptide library was screened to identify the B cell epitope of anti-βィイD22ィエD2-GPI antibodies established from APS patients. Putative epitopes were identified on domain IV of the βィイD22ィエD2-GPI protein.iii) Among the known polymorphisms of βィイD22ィエD2-GPI, ィイD1247ィエD1Val/Leu polymorphism was associated with prevalence of anti-βィイD22ィエD2-GPI antibodies. A monoclonal anti-βィイD22ィエD2-GPI antibody was found to bind to ィイD1247ィエD1ValβィイD22ィエD2-GPI more strongly than to ィイD1247ィエD1LeuβィイD22ィエD2-GPI.iv) Peripheral blood T lymphocytes from APS were tested for their response against ィイD1247ィエD1ValβィイD22ィエD2-GPI and ィイD1247ィエD1LeuβィイD22ィエD2-GPI. A large heterogeneity was observed among individual patients, suggesting the importance of this polymorphism in βィイD22ィエD2-GPI induced T cell response.v) Two families with βィイD22ィエD2-GPI deficiency were identified. βィイD22ィエD2-GPI deficient individuals had a homozygous deletion in the 4ィイD1thィエD1 exon of βィイD22ィエD2-GPI. βィイD22ィエD2-GPI deficient individuals did not show significant abnormalities in hemostasis or lipid metabolism. Persons with hetorozygous deficiency were found in 6.3% of the studied population.

1）从抗磷脂综合征（antiphospholipid syndrome，APS）患者外周血淋巴细胞中制备抗β-内酰胺D22-GPI和抗凝血酶原单克隆抗体。2）从随机肽库中筛选抗β-内酰胺D22-GPI单克隆抗体的B细胞表位。在β-内酰胺D22内酰胺D2-GPI蛋白的结构域IV上鉴定了推定的表位。iii）在已知的β-内酰胺D22内酰胺D2-GPI多态性中，内酰胺D1247内酰胺D1 Val/Leu多态性与抗β-内酰胺D22内酰胺D2-GPI抗体的流行相关。发现单克隆抗-β CD 22 β CD 2-GPI抗体与β CD 1247 β CD 1Val β CD 22 β CD 2-GPI的结合比与β CD 1247 β CD 1 Leu β CD 22 β CD 2-GPI的结合更强。iv）测试来自APS的外周血T淋巴细胞对β CD 1247 β CD 1Val β CD 22 β CD 2-GPI和β CD 1247 β CD 1 Leu β CD 22 β CD 2-GPI的应答。在个体患者中观察到很大的异质性，这表明该多态性在β 2-D22-GPI诱导的T细胞应答中的重要性。v）鉴定了两个具有β 2-D22-GPI缺陷的家族。β 2 2受体D2-GPI基因缺失者的β 2 2受体D2-GPI基因第4外显子D1位D1为纯合性缺失。β 2-D22受体D2-GPI缺乏的个体在止血或脂质代谢方面没有表现出显著的异常。杂合子缺陷的人被发现在6.3%的研究人群。