ALLOTYPE LINKED RESISTANCE TO HERPES STROMAL KERATITIS

描述（改编自研究者摘要）：基因多态性 一般认为， 通过它们的蛋白质产物而不是来自 他们 研究人员最近的研究表明，基因多态性可以 还通过改变耐受T细胞的自身肽的结构起作用。 研究人员发现，免疫球蛋白连锁的HSK耐药是由 通过IgG 2ab衍生的抗原肽而不是完整的IG 分子。 此外，对HSK的抗性与HSK基因的表达有关。 IgHb同种异型也可以通过暴露于可溶性 IgG2ab衍生肽在成年生活中的作用。 为了定义细胞事件 导致自身耐受或病毒诱导的自身免疫， 将产生携带转基因TCR的小鼠，所述转基因TCR由致病性 小鼠CD4克隆，他们已经表征。 这些动物，沿着着 适当的血清学试剂，将用于提供洞察， 胸腺内选择和外周反应性潜在的角化 敏感和耐药菌株中的T细胞克隆， 涉及缺失和/或无反应性的机制负责自我耐受性。 此外，他们将充分评估HSV-1在诱导 自身免疫性疾病，特别注意HSV-1 可以模拟角膜自身抗原。 最后，他们将进一步澄清 通过更精确地定义肽， 来源于调节HSK的IgG2ab。 作用方面的信息 免疫球蛋白衍生肽对TCR转基因小鼠胸腺细胞发育的影响 有助于阐明内源性基因产物可以 影响胸腺细胞选择以及对 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.