THE FAMILY OF KAPPAB REGULATORS FOR GENES IN THE IMMUNE RESPONSE

几种淋巴因子和其他分子的基因调控 参与免疫应答的DNA依赖于一个10 bp的DNA序列， 卡帕 这个序列结合了一个不断增长的核蛋白家族， 其中一些与rel癌基因有关， 严格控制这些基因的转录。 重要的是，KappaB 在人类免疫缺陷病毒（HIV）中发现了该序列。 把握的根本 KappaB序列的特征是它允许在一个转录水平上转录。 高度调节的方式-时间上和适当的细胞类型， 特定基因 我们正试图阐明这一特定的 规则发生。 我们已经发现IL-2受体α链基因 增强子通过NF-KappaB的合作在T细胞中特异性地起作用 另一种基因调节蛋白叫SRF。 我们还发现， KappaB位点具有调控意义。 通过学习正常 非转化的T淋巴细胞克隆，我们发现了一种新的核 复合物，称为NF-CYT 1，优先与KappaB位点相互作用 在白细胞介素2基因中。 NF-CYT 1的存在，在一些 不同生物学条件与IL-2基因表达呈负相关 在T细胞中的表达。 这表明它可能是一种负调节剂。 非常重要的是，该因子与HIV的增强子区域结合。 我们 假设它可能在抑制HIV病毒转录方面发挥作用 静息T细胞 我们还确定了NF-κ B的激活 可以在T细胞的抗原刺激期间发生，而不依赖于T细胞 细胞受体信号传导

Regulation of genes for several lymphokines as well as other molecules involved in the immune response depend on a 10 bp DNA sequence termed, KappaB. This sequence binds a growing family of nuclear proteins, several of which are related to the rel oncogene, that are capable of tightly governing transcription of these genes. Importantly, the KappaB sequence is found in the human immunodeficiency virus (HIV). A cardinal feature of the KappaB sequence is that it permits transcription in a highly regulated fashion- temporally and in appropriate cell-types for specific genes. We are attempting to elucidate how this specific regulation occurs. We have found the IL-2 receptor alpha chain gene enhancer acts specifically in T cells through cooperation of NF-KappaB and another gene regulatory protein called SRF. We have also found that the microheterogeneity in DNA sequence among KappaB sites has regulatory significance. By studying normal non-transformed T lymphocyte clones we discovered a novel nuclear complex, termed NF-CYT1 that interacts preferentially with a KappaB site in the interleukin-2 gene. Tbe presence of NF-CYT1 in a number of different biological conditions is inversely correlated with IL-2 gene expression in T cells. This suggests it may be a negative regulator. Very significantly, this factor binds to the enhancer region of HIV. We postulate it may have a role in suppressing HIV viral transcription in resting T cells. We also have determined that activation of NF-KappaB can occur during antigenic stimulation of T cells independently of T cell receptor signalling.