FACTORS CONTROLLING GRAFT-HOST INTERACTIONS

对异基因造血移植物的天然抵抗力，特别是F1 对亲本嫁接的杂交抗性，代表了 令人费解的免疫现象。这种抵抗力是遗传的 特定的，以非共显性遗传模式为特征的， 主要组织相容性复合体(MHC)控制。这个 效应机制由自然杀伤细胞(NK细胞)介导， 因此，抗辐射的和预先存在的。这些属性是 独特的，不容易与当代概念相协调的 细胞免疫学和移植遗传学。长的- 这项研究项目的学期目标是阐明 免疫遗传、细胞和最终的分子机制 隐藏在天然抵抗力之下。 这项申请提出了一种接近分子的方法 对细胞表面靶结构的理解 在F1对亲本H-2b/HH-1b的抗性中识别 造血移植物。研究主要是为了测试 假设抗杂化的靶结构是 低聚糖。缺乏这些基因的淋巴瘤细胞克隆 决定因素将由1)抗性F1特异性地选择 体内杂交宿主和2)体外非特异性选择 细胞表面寡糖发生变化的变异体。体细胞 杂交将被用来研究遗传损伤的性质 变异克隆。几种糖基化抑制剂的作用 关于HH-1b决定簇的表达将被检测和HH-1b 对阳性克隆和阴性克隆进行生化比较。这些 研究对于更好地理解NK的作用是必不可少的 在正常造血中的细胞，在免疫监测中 造血肿瘤，以及在骨髓移植失败中 天哪。

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.