DELINEATION OF IMMUNE RECOGNITION OF HUMAN IA

这项提案的总体目标是定义抗原性， 人Ia抗原的同种异体识别和功能位点 预先确定的特异性抗体，即针对小分子合成抗体 由这些氨基酸序列的亲水区组成的多肽 抗原。将努力描绘出人类白细胞抗原-DR2的这些区域 构成抗原性位点的β链以及 参与表达这种病毒的血清学定义的多态 分子。还将尝试确定这些抗原性位点 通过使用抗体区分人类白细胞抗原-DR和人类白细胞抗原-DC 不同的人类白细胞抗原-树突状细胞α链结合多肽和 与适当靶细胞的结合抑制试验和纯化 抗原。第三个主要目的是使用这些预先确定的抗体 描述人Ia抗原功能区的特异性。这 将通过确定小的合成肽是否 由人类白细胞抗原-DR和人类白细胞抗原-DC的特定区域组成可以完整地模拟 IA分子作为同种异体反应性T细胞克隆的刺激因子 针对这些多肽的抗体可以抑制克隆的反应。 IA限制性T细胞株。预计这些研究将有助于 为了更好地理解小学和小学之间的关系 人Ia抗原的结构及其在免疫反应中的作用。

The overall objective of this proposal is to define the antigenic, allorecognition and functional sites of human Ia antigens by using antibodies of predetermined specificity, i.e. directed to small synthetic peptides comprising hydrophilic regions of the amino acid sequence of these antigens. An effort will be made to delineate those regions of the HLA-DR2 Beta chain which constitute antigenic sites as well as those that are involved in expressing the serologically defined polymorphism of this molecule. An attempt will also be made to define those antigenic sites which distinguish HLA-DR from HLA-DC antigens by using antibodies to distinct peptides of Alpha chain of HLA-DC antigens in binding and inhibition of binding assays against appropriate target cells and purified antigens. A third major aim is to use these antibodies of predetermined specificity to delineate functional regions of human Ia antigens. This will be accomplished by determining whether small synthetic peptides comprising defined regions of HLA-DR and HLA-DC antigens can mimic intact Ia molecules as stimulators of alloreactive T cell clones and whether antibodies directed to these peptides can inhibit the response of cloned Ia-restricted T cell lines. It is anticipated that these studies will aid in providing a better understanding of the relationship between primary structure of human Ia antigens and their functions in the immune response.