ALLOTYPE LINKED RESISTANCE TO HERPES STROMAL KERATITIS

描述(改编自调查者摘要)：基因的多态 影响自身免疫性疾病抵抗力的因素被普遍认为 通过他们的蛋白质产品而不是通过从 他们。研究人员最近的研究表明，基因多态可以 也可以通过改变耐受T细胞的自体多肽的结构来起作用。 研究人员发现，对HSK的免疫球蛋白连锁抗性是由 通过IgG2ab衍生的抗原肽而不是完整的Ig 分子。此外，对HSK的抗性与HSK的基因表达有关 Ighb同种异型也可以通过接触可溶性的 成人生活中的IgG2ab衍生肽。为了定义蜂窝事件 导致自我耐受或病毒诱导的自身免疫，研究人员 会产生携带转基因TCR的小鼠，显示出致病性 他们所描述的小鼠的CD4克隆。这些动物，以及 适当的血清学试剂，将用于提供对 潜在角化原性胸腺内选择和外周反应性 敏感和耐药品系的T细胞克隆及鉴定 涉及缺失和/或无能的机制导致自我耐受。 此外，他们还将充分评估HSV-1在诱导 自身免疫性疾病，特别注意HSV-1 可能模仿一种角膜自身抗原。最后，他们将进一步澄清 通过更准确地定义多肽来确定这种反应的结构基础 来源于调节HSK的IgG2ab。关于以下影响的信息 免疫球蛋白衍生肽对TCR转基因小鼠胸腺细胞发育的影响 帮助描绘内源性基因产物可以 既影响胸腺细胞的选择，也影响对An的敏感性 自身免疫性疾病。

DESCRIPTION (Adapted from Investigator's abstract): Polymorphisms of genes which influence resistance to autoimmune disease have generally been thought to act through their protein products rather than peptides derived from them. The investigator's recent studies show that genetic polymorphisms can also act by changing the structure of self-peptides which tolerize T-cells. The investigators have found that Ig-linked resistance to HSK is mediated through an IgG2ab-derived antigenic peptide rather than the intact Ig molecule. Moreover, resistance to HSK associated with genetic expression of the Ighb allotype can also be conferred by exposure to soluble IgG2ab-derived peptides in adult life. To define the cellular events leading to self-tolerance or viral-induced autoimmunity, the investigators will generate mice carrying a transgenic TCR displayed by the pathogenic murine CD4 clones that they have characterized. These animals, along with appropriate serologic reagents, will be used to provide insight into intrathymic selection and peripheral reactivity of potentially keratogenic T-cell clones in susceptible and resistant strains and to determine mechanisms involving deletion and/or anergy responsible for self-tolerance. In addition, they will fully evaluate the role of HSV-1 in the induction of autoimmune disease, with particular attention to the possibility that HSV-1 may mimic a corneal autoantigen. Finally, they will further clarify the structural basis of this response by defining more precisely the peptides derived from IgG2ab which regulate HSK. Information on the effects of Ig-derived peptides on thymocyte development in TCR transgenic mice should help delineate the mechanisms by which endogenous gene products can influence both thymocyte selection as well as susceptibility to an autoimmune disorder.