FUNCTION/REGULATION OF HLA ANTIGENS ON CULTURED CELLS

HLA 抗原对培养细胞的功能/调节

• 批准号: 3180670
• 负责人: MARILYN S POLLACK
• 金额: $ 9.18万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-04-01 至 1989-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3180670
• 关键词: T lymphocyte; autoimmune disorder; cancer registry /resource; cell cell interaction; cell differentiation; cell type; clone cells; fibroblasts; flow cytometry; gene expression; graft versus host disease; helper T lymphocyte; histocompatibility gene; histocompatibility typing; human tissue; interleukin 2; mixed tissue /cell culture; monoclonal antibody; neoplasm /cancer immunology; neoplastic cell culture for noncancer research; prostaglandins; suppressor T lymphocyte

This project involves studies of the comparative functional and biochemical properties and the regulation of expression of Class II histocompatibility (HLA) determinants on different types of cultured human cells. The Principal Investigator has extensive experience with the technical aspects of serological and cellular HLA allotyping of cultured human cells, with conducting functional studies of their HLA antigens, and with inducing the expression of Class II antigens on cultured cells that do not already express them. These studies already helped establish that human tumor cell lines express genetically appropriate HLA A,B,C and, in some cases, DR antigens; that induction of Class II antigens can occur with differential expression of different Class II antigen types on some normal and tumor cell lines; and, that the Class II alloantigens expressed on some cell lines fail to act as strong stimulators of primary allogeneic proliferative or cytolytic responses but can act as secondary stimulators and as targets of cytolytic responses. The proposed studies will continue and expand the previous studies in order to determine the basis and the significance of these and other functional differences between the histocompatibility antigens on different cell types. The studies will use naive allogeneic responder T-cells and cloned responder T-cells with known specificity for particular allogeneic HLA antigens or hapten-modified self-HLA antigens; monoclonal antibodies to T-cell differentiation antigens and particular Class II (DR, DQ or DP) determinants; cytofluorograph and cell sorting techniques to select subpopulations of stimulator cells with particularly disparate Class II antigen pattern differences; biochemical techniques; and soluble leukocyte response mediators to determine whether differences in functional activities can be attributed to differences in quantitative, qualitative, or biochemical characteristics of the stimulatory cells' native or induced Class II HLA determinants. These studies will collectively improve our understanding of the role that histocompatibility determinants may play in the induction of auto immune disease responses, in the induction of graft vs. host responses and graft rejection, in the immune response of tumor patients to their own tumors, and our understanding of the regulation and function of different HLA antigens in normal cell-cell interactions.

该项目涉及比较功能和生化的研究 II类组织相容性的特性和表达调节 (HLA) 不同类型培养人类细胞的决定因素。 这 首席研究员在技术方面拥有丰富的经验 对培养的人类细胞进行血清学和细胞 HLA 同种异型分析， 对其 HLA 抗原进行功能研究，并诱导 II 类抗原在尚未表达的培养细胞上表达 表达它们。 这些研究已经帮助确定人类肿瘤细胞 细胞系表达遗传上适当的 HLA A、B、C，在某些情况下还表达 DR 抗原； II类抗原的诱导可以通过不同的方式发生 不同II类抗原类型在一些正常和肿瘤上的表达 细胞系；并且，II类同种抗原在某些细胞上表达 细胞系不能作为原代同种异体增殖的强刺激剂 或细胞溶解反应，但可以作为次级刺激剂和靶标 细胞溶解反应。 拟议的研究将继续并扩大 以前的研究，以确定基础和意义 这些和其他功能差异之间的组织相容性 不同细胞类型上的抗原。 该研究将使用幼稚的同种异体 应答 T 细胞和具有已知特异性的克隆应答 T 细胞 特定的同种异体HLA抗原或半抗原修饰的自身HLA抗原； 针对 T 细胞分化抗原的单克隆抗体，特别是 II 类（DR、DQ 或 DP）决定因素；细胞荧光照片和细胞分选 选择刺激细胞亚群的技术，特别是 不同的 II 类抗原模式差异；生化技术；和 可溶性白细胞反应介质以确定是否存在差异 功能活动可归因于数量上的差异， 刺激细胞的定性或生化特征 天然或诱导的 II 类 HLA 决定簇。 这些研究将 共同提高我们对组织相容性作用的理解 决定因素可能在诱导自身免疫疾病反应中发挥作用， 诱导移植物抗宿主反应和移植物排斥 肿瘤患者对其自身肿瘤的免疫反应，以及我们的 了解不同HLA抗原的调节和功能 正常的细胞间相互作用。