FACTORS CONTROLLING GRAFT-HOST INTERACTIONS

对造血同种异体移植物的天然抗性，特别是F1 杂种对亲本嫁接的抗性，代表了 令人困惑的免疫学现象 抵抗是遗传的 特异性，以非共显性遗传方式为特征， 和主要组织相容性复合体（MHC）控制。 的 效应机制由自然杀伤（NK）细胞介导，并且 因此是抗辐射的和预先存在的。 这些属性 独特的，不容易与当代概念调和 细胞免疫学和移植遗传学。 很长的- 本研究项目的长期目标是阐明 免疫遗传、细胞和最终分子机制 这是自然抵抗的基础。 本申请提出了一种朝向分子生物学的方法。 了解细胞表面的目标结构， 在F1杂种对亲本H-2b/Hh-1b的抗性中被识别 造血移植物 研究主要是为了测试 假设杂交抗性的靶结构是 低聚糖。 淋巴瘤细胞的克隆缺乏这些 决定因素将被选择1）具体由抗性F1 体内杂交宿主和2）通过选择非特异性体外杂交宿主， 具有改变的细胞表面寡糖的变体。 体细胞 杂交将用于研究遗传病变的性质， 变异克隆 选择的糖基化抑制剂的作用 对Hh-1b决定簇表达的影响将进行测试， 对阳性和阴性克隆进行生物化学比较。 这些 研究对于更好地理解NK的作用至关重要 细胞在正常造血，在免疫监视， 造血系统肿瘤和骨髓移植失败， 伙计

Natural resistance to hemopoietic allografts, in particular F1 hybrid resistance to parental grafts, represents one of the most puzzling immunological phenomena. The resistance is genetically specific, characterized by a noncodominant mode of inheritance, and major histocompatibility complex (MHC)-controlled. The effector mechanism is mediated by natural killer (NK) cells, and hence radio-resistant and preexisting. These properties are unique, and not easily reconciled with the contemporary concepts of cellular immunology and transplantation genetics. The long- term objective of this research project is to elucidate the immunogenetic, cellular, and ultimately molecular mechanisms underlying the natural resistance. This application proposes an approach towards a molecular understanding of the cell surface target structures that are recognized in F1 hybrid resistance to parental H-2b/Hh-1b hemopoietic grafts. Studies are designed primarily to test the hypothesis that the target structures for hybid resistance are oligosaccharides. Clones of lymphoma cells lacking these determinants will be selected 1) specifically by resistant F1 hybrid hosts in vivo and 2) nonspecifically in vitro by selecting variants with altered cell surface oligosaccharides. Somatic cell hybridization will be used to study the nature of genetic lesions in the variant clones. The effect of selected glycosylation inhibitors on the expression of Hh-1b determinants will be tested and Hh-1b positive and negative clones biochemically compared. These studies are essential for a better understanding of the role of NK cells in normal hemopoiesis, in immune surveillance for hemopoietic neoplasms, and in bone marrow allograft failure in man.