FUNCTION/REGULATION OF HLA ANTIGENS ON CULTURED CELLS

该项目涉及比较功能和生物化学的研究， II类组织相容性的性质和表达调控 (HLA)不同类型的人类培养细胞的决定因素。 的 主要研究者在技术方面具有丰富的经验 对培养的人类细胞进行血清学和细胞HLA同种异型分型， 进行其HLA抗原的功能研究，并诱导 在培养的细胞上表达II类抗原， 表达他们。 这些研究已经帮助建立了人类肿瘤细胞 细胞系表达遗传上合适的HLA A、B、C，在某些情况下，表达DR 抗原; II类抗原的诱导可以发生与分化 不同Ⅱ类抗原在正常组织和肿瘤组织中的表达 细胞系;并且，II类同种抗原在某些细胞上表达 细胞系不能作为原发性同种异体增殖性淋巴瘤的强刺激物， 或细胞溶解反应，但可作为次级刺激物和靶点 细胞溶解反应。 拟议的研究将继续进行，并扩大 以前的研究，以确定的基础和意义， 这些和其他功能上的差异 不同细胞类型的抗原。 这些研究将使用未经处理的同种异体 应答T细胞和克隆的应答T细胞，其具有已知的特异性， 特定的同种异体HLA抗原或半抗原修饰的自身HLA抗原; 抗T细胞分化抗原的单克隆抗体， II类（DR、DQ或DP）决定簇;细胞荧光检查和细胞分选 选择刺激细胞亚群的技术， 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，以确定是否差异， 功能活动可以归因于数量上的差异， 刺激细胞的定性或生物化学特征 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 决定因素可能在诱导自身免疫疾病反应中起作用， 诱导移植物抗宿主反应和移植物排斥反应， 肿瘤患者对自身肿瘤的免疫反应， 了解不同HLA抗原的调节和功能， 正常的细胞间相互作用

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.