IMMUNOGENETICS OF HYBRID RESISTANCE

长期目标是确定表达的遗传机制 白血病和白血病细胞表面的造血组织相容性 (Hh) 抗原 正常祖细胞并表征 Hh 分子本身。 至 为此，描述了以下目标： 1. 确认以下结论： 淋巴瘤细胞上的 Hh 抗原表达被“下调” 反式作用调节基因。 使用体内和体外测定 可以测量“冷靶细胞竞争”的杂交抗性， 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. 更精确地绘制 Hh 基因图谱。 B10.RQDB是一个新的 Chella David 描述的 H-2 重组体，表达 Dd、Db，但不表达 LD。 因此，D 和 L 之间发生重组，Db 确实发生了重组。 磅。 骨髓细胞失去了 Hhb，为同种异体宿主保留了 Hhd，并且 F1 杂交宿主的 Hhd 降低。 还有其他新的重组体 将用于映射 Hh，它应该与 L 相反，因为序列 是 D 区中的 D (R) L。 (3)检验顺式基因假设，即 邻近基因调节 Hh 表达。 使用相同的新 H-2 重组 检测 S 和 L 之间可能调节 Hh 表达的基因 调节对亲本 Hh 抗原的“耐受性”的杂合子。 (4) 继续检验杂种的“同种异体抑制”假说 阻力。 来自 C.B-17 scid/scid 供体的骨髓细胞，不能 产生同种异体反应性 T 或 B 细胞，但会被辐射排斥 同种异体或 F1 杂交受体小鼠。 (5) 表征 Hh 分子。 35S-蛋氨酸标记的 EL-4 和各种 ACCb 细胞裂解物的二维凝胶 线，然后对射线照片进行计算机分析，确定了 90 kd 分子作为 Hhb 抗原的潜在候选者。 我们将生成 抗体分离分子并研究其结构。

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.