IMMUNOGENETICS OF HYBRID RESISTANCE

混合抗性的免疫遗传学

• 批准号: 3174577
• 负责人: Michael Bennett
• 金额: $ 8.79万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-03-01 至 1990-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3174577
• 关键词: antibody dependent killer cell; autoimmune disorder; bone marrow transplantation; cell fusion; clone cells; gene dosage; gene expression; genetic mapping; genetic regulation; graft versus host disease; haploidy; heterozygote; histocompatibility antigens; immune tolerance /unresponsiveness; immunoglobulins; immunoregulation; laboratory mouse; laboratory rat; major histocompatibility complex; monoclonal antibody; neoplasm /cancer immunology; newborn animals; radiation immunosuppression; structural genes

The long-term goal is to determine the genetic mechanism of expression of Hemopoietic histocompatibility (Hh) antigens on the surface of leukemic and normal progenitor cells and characterize the Hh molecules themselves. To that end the following Aims are described: 1. Confirm the conclusion that Hh antigenic expression on lymphoma cells is "down-regulated" by trans-acting regulatory genes. Using both in vivo and in vitro assays for hybrid resistance in which "cold target cells competition" can be measured, we observed that ACCb H-2d/H-2b loss mutants which had lost Dd gained the expression of Hhb. 2. Map the Hh genes more precisely. B10.RQDB is a new H-2 recombinant described by Chella David, which expresses Dd, Db, but not Ld. Therefore, recombination occurred between D and L and Db is really Lb. The marrow cells have lost Hhb, retained Hhd for allogenic hosts and have decreased Hhd for F1 hybrid hosts. There and other new recombinants will be used to map Hh, which should be contromeric to L since the sequence is D (R) L in the D-region. (3) Test the cis gene hypothesis, i.e. an adjacent gene regulates Hh expression. Use same new H-2 recombination to detect gene(s) between S and L which may regulate Hh expression in heterozygotes that regulated "tolerance" to parental Hh antigen. (4) Continue to test the "allogenic inhibition" hypothesis for hybrid resistance. Marrow cells from C.B-17 scid/scid donors, which cannot generate alloreactive T or B cells, nevertheless are rejected by irradiated allogeneic or F1 hybrid recipient mice. (5) Characterize Hh molecules. 2-D gels of lysates of 35S-methionine labeled EL-4 and various ACCb cell lines, followed by computer analysis of radiographs, identified a 90 kd molecule as a potential candidate for the Hhb antigen. We will generate antibodies to isolate the molecules, and study its structure.

长期的目标是确定基因表达的机制 白血病细胞表面的造血组织相容性(HH)抗原 并对HH分子本身进行鉴定。至 为此，描述了以下目标：1.确认结论 HH抗原在淋巴瘤细胞上的表达被下调 反式调节基因。使用体内和体外检测方法 杂交抗性，其中“冷靶细胞竞争”可以被测量， 我们观察到失去DD的ACCB H-2d/H-2b缺失突变体获得了 HHB的表达。2.更加精确地定位HH基因。B10.RQDB是一种新的 Chella David描述的H-2重组体，表达DD、DB，但不表达 身份证。因此，D和L之间的重组和DB之间的重组真的是 磅。骨髓细胞失去了HHb，为同种异体宿主保留了HHD 降低了F1杂交寄主的HHD。那里和其他新的重组体 将被用来映射HH，这应该是控制L的序列 D(右)L在D区。(3)检验顺式基因假说，即 邻近基因调控HH的表达。使用相同的新H-2重组来 检测S和L之间可能调节HH表达的基因(S) 调节对亲本HH抗原的“耐受性”的杂合子。(4) 继续检验杂交种的“同种异体抑制”假设 抵抗。来自C.B-17 SCID/SCID捐赠者的骨髓细胞，不能 产生同种异体反应的T或B细胞，但被辐射排斥 同种异体或F1杂交受体小鼠。(5)HH分子的表征。 标记EL-4的35S-蛋氨酸裂解产物与不同ACCB细胞的二维凝胶 线条，然后对射线照片进行计算机分析，确定了90kd 分子作为HHB抗原的潜在候选者。我们将生成 抗体来分离分子，并研究其结构。