ANTIGEN PRESENTATION--MODEL OF ALLERGIC EYE DISEASE

抗原呈递——过敏性眼病模型

• 批准号: 6384800
• 负责人: Santa Jeremy Ono
• 金额: $ 30.22万
• 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/6384800
• 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.

直接过敏或过敏是最广泛的 人类的免疫障碍。我们最近开发了一只鼠标 过敏性结膜炎的模型（FEL DL）和 表征了易感动物的T辅助反应。 大约25％的世界人口遭受过敏；和 眼部症状造成了很大比例的不适 以及与过敏性疾病有关的患者护理费用。有 眼科医生对发展的兴趣很大 可以安全地使用的抗过敏和抗炎化合物 眼睛。一种新颖而有希望的管理方法 过敏性疾病是肽免疫疗法。识别 基于原发性的定义的含有肽的T细胞表位 主要过敏原的结构可以为 修饰人类对过敏原的过敏性。自从 功能和生化研究表明，这一代 T细胞反应的取决于T细胞上的抗原受体（TCR） 识别与外来蛋白质的肽片段 主要组织相容性复合物（MHC）的产品， 在辅助细胞的膜上表达，任何对T细胞的检查 表位还必须包括MHC分析。因此，目标的目标 建议是使用我们的小鼠过敏性结膜炎模型清楚 定义分子相互作用 免疫主导肽，抗原呈现细胞（APC）上的MHC， 和T细胞受体。在定义特定t之后 单元/肽/APC相互作用，我们将使用此信息开发 新型T细胞疫苗我做抗原化的MHC-Ig嵌合体，然后 在我们的小鼠过敏模型中测试该T细胞疫苗 结膜炎。