FUNCTION/REGULATION OF HLA ANTIGENS ON CULTURED CELLS

本项目涉及比较功能和生化的研究。 第II类组织相容性的性质及其表达调控 不同类型培养的人类细胞上的(HL A)决定因素。这个 首席调查员在技术方面有丰富的经验 培养的人类细胞的血清学和细胞人类白细胞抗原同种异型， 对它们的人类白细胞抗原进行功能研究，并通过诱导 II类抗原在尚未表达的培养细胞上的表达 把它们表达出来。这些研究已经帮助确定了人类肿瘤细胞 这些株系表达遗传上合适的HLAA、B、C，在某些情况下，还表达DR 抗原；诱导II类抗原可在不同的情况下发生 不同类型II类抗原在某些正常组织和肿瘤组织中的表达 在某些细胞上表达II类同种异体抗原 LINE不能作为初级同种异体增殖的强刺激因子 或细胞溶解反应，但可作为次级刺激因子和靶子 细胞溶解反应。拟议的研究将继续进行，并扩大 为了确定前人研究的依据和意义 这些与其他组织相容性之间的功能差异 不同细胞类型上的抗原。这些研究将使用幼稚的同种异体 应答T细胞和克隆的应答T细胞具有已知的特异性 特定的同种异体人类白细胞抗原或半抗原修饰的自身人类白细胞抗原； 抗T细胞分化抗原和特异性抗原的单抗 II类(DR、DQ或DP)决定因素；细胞荧光摄影术和细胞分选 选择刺激细胞亚群的技术，特别是 完全不同的II类抗原模式差异；生化技术；以及 确定可溶性白细胞反应介质是否存在差异 功能性活动可以归因于数量上的差异， 刺激细胞的定性或生化特征 天然或诱导的第二类人类白细胞抗原决定簇。这些研究将 共同提高我们对组织相容性的作用的理解 决定因素可能在诱导自身免疫性疾病反应中发挥作用 移植物对宿主的反应和移植物排斥反应的诱导 肿瘤患者对自身肿瘤的免疫反应，以及我们的 对不同人类白细胞抗原的调节和作用的认识 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.