REQUIREMENTS FOR CLASS I RESTRICTED E CELL RECOGNITION OF ANTIGEN

I 类限制性 E 细胞识别抗原的要求

• 批准号: 3814498
• 负责人: HOWARD M GREY
• 金额: --
• 依托单位: NATIONAL JEWISH HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3814498
• 关键词: B lymphocyte; T cell receptor; T lymphocyte; antigen presentation; antigen presenting cell; cytotoxic T lymphocyte; dendritic cells; erythrocyte membrane; gel filtration chromatography; gene expression; genetic manipulation; histocompatibility antigens; laboratory mouse; macrophage; microinjections; ovalbumin; protein structure function; receptor binding

While there is data to suggest that both class I and II_restricted antigenic determinants are present on short peptides, little more is known about the mechanism of antigen processing and presentation for class I restricted recognition of antigen. Our preliminary data indicate that class I-restricted cytolytic T cells (CTL) cAn be generated to the soluble protein antigen ovalbumin (OVA) when the antigen is used in the form of peptides present in a OVA tryptic digest but not when used as an intact protein. We will use OVA, which is well characterized with respect to the processing and presentation pathway for class II restricted responses and which is available in large quantities in pure forms, as a model to investigate the processing and presentation of antigen in the context of class I molecules. The parameters that influences the ability of OVA to induce class I-restricted CTL activity in vivo will be investigated in order to determine whether antigenic peptides can be administered directly to the animal or whether there is a need for an antigen "priming" cell. We will determine if the presence of an antigen containing a "helper determinant", perhaps linked to the class I-restricted determinant, enhances CTL priming. We will define the peptides within OVA that generate class I restricted responses and investigate the capacity of these peptides to form complexes with their class I restriction elements. Finally, we will investigate whether antigen processing for the generation of class I vs. class II restricted determinants involve the same or different metabolic pathways.

虽然有数据表明，I类和II类受限制 抗原决定簇存在于短肽上， 已知抗原加工和呈递的机制 用于抗原的I类限制性识别。 我们的初步 数据表明，I类限制性溶细胞性T细胞（CTL）cAn 产生可溶性蛋白抗原卵清蛋白（OVA）， 抗原以存在于OVA中的肽的形式使用 胰蛋白酶消化物，但当作为完整蛋白质使用时则不是。 我们将使用 OVA，其在加工方面具有良好的特征， II类限制性反应的呈现途径， 作为一种模型， 研究抗原的加工和呈递， I类分子的背景。 影响卵清蛋白诱导类分化能力的参数 将研究体内I-限制性CTL活性，以 确定抗原肽是否可以直接施用 或者是否需要抗原“引发” cell. 我们将确定是否存在含有 一个“辅助决定簇”，也许与I类限制性的 决定子，增强CTL引发。 我们将定义肽 在OVA中，产生I类限制性反应， 研究这些肽形成与 I类限制元素 最后，我们将调查 抗原处理是否用于生成I类与 II限制性决定因素涉及相同或不同的代谢 途径。