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: 3803432
• 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/3803432
• 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类都受到限制 抗原决定簇存在于短肽上，仅此而已。 已知抗原处理和提呈的机制 对于I类，限制了抗原的识别。我们的预赛 数据表明，I类限制性细胞溶解T细胞(CTL)可以 当产生可溶性蛋白抗原卵清蛋白(OVA)时 这种抗原是以卵子中存在的多肽的形式使用的 胰酶消化，但不能作为完整的蛋白质使用。我们将使用 卵子，它的特点是很好的加工和 第II类限制性反应的呈递途径 以纯形式大量提供，作为模型以 研究抗原在体内的加工和提呈 第I类分子的背景。 影响卵清蛋白诱导课能力的参数 将对体内I-限制性CTL活性进行研究，以便 确定抗原肽是否可以直接给药 或者是否需要抗原“预置” 手机。我们将确定是否存在一种含有 一个“辅助行列式”，可能与类i-受限有关 决定簇，增强CTL启动。我们将定义这些多肽 在OVA中，生成I类受限响应 研究这些多肽与蛋白质形成络合物的能力。 他们的I类限制元素。最后，我们将调查 抗原处理是否为第I类与第I类 Ii限制性决定因素涉及相同或不同的代谢 小路。