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首页> 外文学位 >Differences between diabetes susceptible and resistant mouse strains in the major histocompatability complex class II mediated antigen processing and presentation of an important pancreatic autoantigen, glutamic acid decarboxylase (GAD-65).
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Differences between diabetes susceptible and resistant mouse strains in the major histocompatability complex class II mediated antigen processing and presentation of an important pancreatic autoantigen, glutamic acid decarboxylase (GAD-65).

机译：在主要的组织相容性复合体II类介导的抗原加工和重要的胰腺自身抗原谷氨酸脱羧酶（GAD-65）的呈递中，对糖尿病易感和耐药的小鼠品系之间的差异。

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摘要

Insulin dependent diabetes mellitus (IDDM) is an autoimmune disease in which destruction of the insulin producing, islet beta cells of the pancreas is mediated by CD4 and CD8 T cells. In young NOD mice, spontaneous B cell and T cell responses to several beta cell antigens, including glutamic acid decarboxylase-65 (GAD-65), arise prior to clinical disease. Susceptibility to IDDM has been linked to as many as 20 genetic loci. The locus conferring greatest susceptibility to IDDM lies within the major histocompatability complex (MHC), indicating that APC and their antigen processing machinery play a central role in the induction of disease. Implied in this view is that one or more of the genetic loci may involve an aspect of antigen processing and presentation.; We studied the role of MHC II mediated antigen processing and presentation of an important diabetogenic autoantigen, GAD-65, in the initiation and propagation of IDDM. APCs from diabetes susceptible (NOD) and resistant (NOR) mice were compared and differences were observed in both the number of GAD-65 determinants presented, and in the relative amount of presentation of a given determinant by APC from the spleens of these two mouse strains. In particular, NOR mice readily presented a determinant from whole GAD-65 (p524-538) to which regulatory T cells have been described, indicating that efficient induction of regulatory T cells may be crucial to protection from disease.; The enhanced antigen processing of GAD-65 determinants by NOR APC was reflected in the heightened natural processing of islet derived GAD-65 ex vivo. Accordingly, presentation of the regulatory determinant p524-538, and the relatively poor presentation of a putatively pathogenic determinant (p530-543) by NOR pancreatic dendritic cells (DC) were observed. In contrast, APC from the spleen of NOD mice failed to present the regulatory p524 determinant. Further, pancreatic DC from NOD mice consistently presented the pathogenic p530 determinant from whole GAD-65 ex vivo. Thus, differences in MHC II mediated antigen presentation of both pathogenic and regulatory beta cell autoantigenic determinants by APC of diabetes susceptible and resistant mouse strains may account, at least in part, for differences in susceptibility to IDDM.
机译：胰岛素依赖型糖尿病（IDDM）是一种自身免疫性疾病，其中胰腺的产生胰岛素的胰岛β细胞的破坏由CD4和CD8 T细胞介导。在年轻的NOD小鼠中，在临床疾病发生之前，对包括谷氨酸脱羧酶-65（GAD-65）在内的几种β细胞抗原的自发性B细胞和T细胞应答。 IDDM的易感性已与多达20个遗传基因座相关。赋予IDDM最易感性的基因位点位于主要组织相容性复合体（MHC）中，表明APC及其抗原加工机制在疾病诱导中起着核心作用。该观点暗示一个或多个遗传基因座可能涉及抗原加工和呈递的一个方面。我们研究了MHC II介导的抗原加工的作用，以及重要的致糖尿病性自身抗原GAD-65在IDDM的起始和繁殖中的作用。比较了来自糖尿病易感（NOD）和抗药性（NOR）小鼠的APC，观察到了GAD-65决定簇的数量以及APC从这两只小鼠脾脏中给定决定簇的相对表达量的差异。株。尤其是，NOR小鼠很容易从描述了调节性T细胞的完整GAD-65（p524-538）中获得一个决定簇，这表明调节性T细胞的有效诱导对于预防疾病至关重要。 NOR APC对GAD-65决定簇的抗原加工增强反映在离体胰岛衍生GAD-65的天然加工增强上。因此，观察到调节决定簇p524-538的呈递，以及NOR胰腺树突状细胞（DC）对假定的致病决定簇（p530-543）的呈递相对较差。相比之下，来自NOD小鼠脾脏的APC无法提供调节性p524决定簇。此外，来自NOD小鼠的胰腺DC始终呈递完整的离体GAD-65致病性p530决定簇。因此，糖尿病易感和耐药小鼠品系的APC在致病性和调节性β细胞自身抗原决定簇的MHC II介导的抗原呈递中的差异可能至少部分解释了对IDDM敏感性的差异。

著录项

  • 作者

    Jensen, Kent Phillip.;

  • 作者单位

    University of California, Los Angeles.;

  • 授予单位 University of California, Los Angeles.;
  • 学科 Health Sciences Immunology.
  • 学位 Ph.D.
  • 年度 2001
  • 页码 190 p.
  • 总页数 190
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 预防医学、卫生学;
  • 关键词

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