REGULATION OF IA GENE EXPRESSION

我们的研究将包括研究小鼠Ia的组织分布 分析Ia特异性信使RNA的存在对基因表达的影响 组织和细胞系。我们将使用来自四个克隆的Ia的DNA探针 基因，A-α，A-β，E-α和E-β，与三个基因结合 敏感的RNA分析、斑点杂交、Northern杂交和S1核酸酶定位， 对能够表达Ia基因的组织以及 它们对Ia基因的诱导能力。S1核酸酶图谱也将是 用于确定是否有任何替代的Ia mRNA加工方法。我们的 研究将确定非骨髓来源细胞的能力 通过产生辐射嵌合体来表达Ia基因。其特点是 IA基因在包括巨噬细胞在内的组织和细胞系中的诱导， 树突状细胞和T细胞将使用已知的诱导剂进行评估 包括伽马干扰素。我们打算批判性地测试最近的 Ia抗原在其他细胞上的移植组织中被诱导的假说 而不是“乘客白细胞”，这是异体移植反应的结果。 最后，我们将研究通过转基因诱导Ia基因的机制。 Ia基因在不同细胞类型中的克隆及诱导物的筛选 表情。(MB)

Our research will include studying the tissue distribution of murine Ia gene expression by analyzing the presence of Ia-specific messenger RNAs in tissues and cell lines. We will use DNA probes derived from four cloned Ia genes, A-alpha, A-beta, E-alpha, and E-beta, in combination with three sensitive RNA assays, dot blots, Northern blots, and S1 nuclease mapping, to critically evaluate the tissues capable of Ia gene expression as well as their capacity for Ia gene induction. S1 nuclease mapping will aIso be used to determine if there is any alternative processing of Ia mRNA. Our investigstion will determine the ability of nonbone marrow-derived cells to express Ia genes by producing radiation chimeras. The characteristics of Ia gene induction in both tissues and cell lines including macrophages, dendritic cells, and T cells will be evaluated using known inducing agents including gamma interferon. We intend to critically test a recent hypothesis that Ia antigens are induced in grafted tissue on cells other than "passenger leukocytes" as a consequence of the allograft reaction. Finally, we will study the mechanism of Ia gene induction by transfecting cloned Ia genes into different cell types and selecting for inducible expression. (MB)