IMMUNOLOGIC STUDY OF HUMAN HLA AND MOUSE H-2 ANTIGENS

目的是获得某些细胞表面标记的精确知识 尤其是淋巴细胞，以及每一种细胞如何作为 分化信号或触发另一个细胞的活动。 大部分 这些努力是针对主要组织相容性的组成部分， 人类的复合体，HLA，包括两种不同类型的抗原，I类 第二类。 只有3个I类分子已被确定，虽然超过 有30个基因。 我们的目标之一是确定是否其他基因在这个 簇（我们称之为同源物）在某些细胞中起作用， 组织，如胸腺或血管内皮，或者如果一些组织仅在 分化的具体阶段。 另一个目标是生产单克隆抗体， I类和II类抗原的抗体。 第二类同系物 包括至少9个功能基因但仅3或4个产物， 可以清楚地区分跨膜糖蛋白异二聚体。 已经产生了针对至少某些个体的单克隆抗体 II类糖蛋白和可能携带的2个或多个表位 我们想知道每个分子是否有各自的功能， 互补问题“同一分子的不同表位是否甚至 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 有些人没有，为什么有些人拒绝肾脏，有些人没有，以及我们如何 通过这种详细的分析，可以了解和控制免疫 在健康和疾病如艾滋病和自身免疫反应。 以来 我们可以通过分析突变细胞来了解细胞功能， 筛选体细胞突变体 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， 我们计划研究小鼠的MHC分子被运送到 吞噬细胞的表面，因为这可能有助于我们了解 高度复杂的分子就像抗原一样。

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.