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。 尤其是那些淋巴细胞，以及每个细胞如何发挥作用 分化发出信号或触发另一个细胞的活动。大部分 这项工作针对主要组织相容性的组成部分 人类的复合体，人类白细胞抗原，包括两种不同类型的抗原，I类 和II类分子。目前只鉴定了3个I类分子 有30个基因存在。我们的目标之一是确定这个基因中的其他基因 簇(我们称之为同系物)在某些细胞中可操作 组织，如胸腺或血管内皮细胞，或者如果有些只在 分化的特定阶段。另一个目标是生产单克隆性 抗第I类和第II类抗原抗体。第二类同类产品 包括至少9个功能基因，但只有3或4个产物， 跨膜糖蛋白异源二聚体可以清楚地区分。 已经产生了对至少部分个体的克隆抗体 II类糖蛋白和可能携带的2个或更多表位 我们希望知道每个分子是否具有不同的功能，并询问 补充问题：同一分子的不同表位是否均匀？ 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会形成抗体 有些人不，为什么有些人排斥肾脏，而另一些人不排斥，以及我们是如何 可以通过这样详细的分析来理解和控制免疫 在健康以及艾滋病和自身免疫等疾病中的反应。自.以来 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。我们还将寻找新的标记 B淋巴细胞和浆细胞。在另一系列的实验中， 小鼠我们计划研究MHC分子被运送到 吞噬细胞的表面，因为这可能有助于我们理解 高度复杂的分子起到了抗原的作用。