IMMUNOLOGIC STUDY OF HUMAN HLA AND MOUSE H-2 ANTIGENS

人 HLA 和小鼠 H-2 抗原的免疫学研究

• 批准号: 3124464
• 负责人: D. BERNARD AMOS
• 金额: $ 34.33万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1974
• 资助国家: 美国
• 起止时间: 1974-10-01 至 1989-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3124464
• 关键词: B lymphocyte; Coxsackievirus; HY antigen; affinity chromatography; antibody dependent killer cell; antibody formation; antibody specificity; antigen antibody reaction; antileukocyte isoantibody; cell sorting; clone cells; electrofocusing; fluorescence; glycoproteins; helper T lymphocyte; histocompatibility antigens; human tissue; hybridomas; immune tolerance /unresponsiveness; immunochemistry; immunodeficiency; isoantibody; laboratory mouse; laboratory rabbit; laboratory rat; lymphoblast; macrophage; major histocompatibility complex; measles; membrane proteins; microorganism classification; monoclonal antibody; mutagens; plaque assay

The objective is to gain precise knowledge of certain cell surface markers especially those of lymphoid cells, and how each can serve as a differentiation signal or trigger the activities of another cell. Most of the effort is directed at components of the major histocompatibility complex of man, HLA, which includes two distinct types of antigen, Class I and Class II. Only 3 Class I molecules have been identified although over 30 genes exist. One of our aims is to determine if other genes in this cluster (which we call a congener) are operational in cells of certain tissue such as thymus or vascular endothelium or if some develop only at specific stages of differentiation. Another aim is to produce monoclonal antibodies to the Class I and Class II antigens. The Class II congener includes at least 9 functioning genes but only 3 or 4 of the products, transmembranous glycoprotein heterodimers can clearly be distinguished. Having produced monoclonal antibodies to at least some of the individual Class II glycoproteins and to the 2 or more epitopes probably carried by each, we wish to know if each molecule has separate function and we ask the complementary question "do the different epitopes of the same molecule even have different function". We believe that the answers to these questions will help us understand why some people form antibodies after transfusion and some do not, why some reject kidneys and others do not, and how we might, through such detailed analyses understand and control immune responses in health and in diseases such as AIDS and autoimmunity. Since we can learn about cellular function by an analysis of mutant cells, we propose to screen for somatic mutants. We shall also look for new markers of B lymphocytes and plasma cells. In a separate series of experiments in mice we plan to study the way that the MHC molecules are transported to the surface of the phagocytic cell since this may help us understand the way that highly complex molecules function as antigens.

目的是获得某些细胞表面标记的精确知识 尤其是淋巴样细胞的人，以及如何用作 分化信号或触发另一个单元的活动。 大多数 这项工作针对主要组织相容性的组成部分 人类的复杂HLA，其中包括两种不同类型的抗原，I类 和II级。 尽管已经确定了3类I类分子 存在30个基因。 我们的目的之一是确定是否有其他基因 群集（我们称为同类物）在某些细胞中运行 组织，例如胸腺或血管内皮，或者仅在 特定的分化阶段。 另一个目的是产生单克隆 I类和II类抗原的抗体。 II级同类 包括至少9个功能基因，但只有3或4个产品， 可以清楚区分透射糖蛋白异二聚体。 产生了至少某些个体的单克隆抗体 II类糖蛋白和2个或更多表位可能由 每个人都希望知道每个分子是否具有分开的功能，我们询问 互补的问题“甚至是同一分子的不同表位 具有不同的功能”。我们相信这些问题的答案 将帮助我们理解为什么有些人在输血后形成抗体 有些人没有，为什么有些人拒绝肾脏和其他人没有，以及我们如何 可以通过这样的详细分析理解和控制免疫 健康和艾滋病和自身免疫等疾病的反应。 自从 我们可以通过分析突变细胞来了解细胞功能，我们 建议筛选体细胞突变体。 我们还将寻找新标记 B淋巴细胞和浆细胞。 在单独的一系列实验中 我们计划研究MHC分子转运到该的小鼠 吞噬细胞的表面，因为这可能有助于我们了解方式 该高度复杂的分子充当抗原。