ANTIGEN PRESENTATION--MODEL OF ALLERGIC EYE DISEASE

抗原呈递——过敏性眼病模型

• 批准号: 6179073
• 负责人: Santa Jeremy Ono
• 金额: $ 19.63万
• 依托单位: SCHEPENS EYE RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6179073
• 关键词: MHC class II antigen; T cell receptor; T lymphocyte; antigen presentation; antigen presenting cell; chimeric proteins; conjunctivitis; disease /disorder model; hypersensitivity; immunoconjugates; immunotherapy; laboratory mouse; leukocyte activation /transformation; tissue /cell culture; vaccine development; vaccines

Immediate hypersensitivity or allergy is the most widespread immunological disorder in humans. We have recently developed a mouse model of allergic conjunctivitis to cat dander (Fel dl), and characterized the T helper responses in susceptible animals. Approximately 25% of the world's population suffer from allergies; with ocular symptoms contributing a significant proportion of the discomfort and patient care costs associated with allergic disease. There is considerable interest among ophthalmologists for the development of new anti-allergic and anti-inflammatory compounds that can be used safely in the eye. A novel and promising approach to management of ongoing allergic disease is that of peptide immunotherapy. Identification of defined T cell epitopes containing peptides, based on the primary structure of major allergens may provide an effective tool for modification of human immediate hypersensitivity to allergens. Since functional and biochemical studies have demonstrated that the generation of T cell responses depends upon antigen receptors on T cells (TCR) recognizing peptide fragments of foreign proteins associated with products of the major histocompatibility complex (MHC), that are expressed on the membranes of accessory cells, any examination of T cell epitopes must also include MHC analysis. Therefore, the goal of this proposal is to use our mouse model of allergic conjunctivitis to clearly define the molecular interaction in the ternary complex of immunodominant peptide, the MHC on the antigen presenting cell (APC), and the T cell receptor. After we have define the specific T cell/peptide/APC interaction, we will use this information to develop a novel T cell vaccine my making an antigenized MHC-Ig chimera, and then to test this T cell vaccine in our mouse model of allergic conjunctivitis.

速发型超敏反应或过敏是最普遍的 人类免疫系统紊乱。我们最近开发了一种老鼠 猫皮屑过敏性结膜炎模型（Fel dl），和 描述了易感动物的辅助性T细胞反应。 大约25%的世界人口患有过敏症; 眼部症状占不适的很大比例 以及与过敏性疾病相关的患者护理费用。有 眼科医生对开发新的 抗过敏和抗炎化合物，可安全用于 the eye.一种新的和有前途的方法来管理正在进行的 过敏性疾病是肽免疫疗法。鉴定 定义的T细胞表位含有肽，基于主要的 主要过敏原的结构可以提供有效的工具， 修饰人对过敏原的速发型超敏反应。以来 功能和生物化学研究表明， T细胞应答的机制依赖于T细胞上的抗原受体（TCR） 识别外源蛋白的肽片段， 主要组织相容性复合体（MHC）的产物， 在辅助细胞的膜上表达，任何T细胞的检查 表位还必须包括MHC分析。因此，这一目标 建议是使用我们的过敏性结膜炎小鼠模型， 定义三元复合物中的分子相互作用 免疫显性肽，抗原呈递细胞（APC）上的MHC， 和T细胞受体。在我们定义了特定的T 细胞/肽/APC相互作用，我们将使用这些信息来开发一个 新型T细胞疫苗可以制造抗原化的MHC-Ig嵌合体，然后 在我们的过敏性小鼠模型中测试这种T细胞疫苗， 结膜炎。