INHERITED CONTROL MECHANISMS IN IG GENE EXPRESSION

这项研究的广泛目标是研究T细胞 对自身和非自身免疫球蛋白的反应。事实上，IgG2a 抗原在已知的Ia B淋巴瘤细胞中自然表达 完全有能力提呈抗原，并且其结构 利用重组DNA技术可以很容易地操纵抗原。 为研究该系统提供了独特的优势。 复杂的细胞内转运途径之间的关系 MHC限制性内切酶特异性。我们计划构建pSV2gt 编码不同形式的C57BL/6 IgG2ab CH3的载体。我们是 对分子的这一部分特别感兴趣，因为 IgH-1b特异性T细胞识别的同种异型决定簇是 位于CH3结构域。可溶性的、膜结合的和细胞质的 表达形式(S)的C57BL/6IgG2ab CH3将在 B淋巴瘤细胞系。我们将对蛋白质产品进行表征 并测试这些分子是否被呈现 至第二类限制性T细胞。一个主要目标是确定 内源性合成的IgG2a抗原是否相互关联 在细胞内与II类分子结合。我们还将表示 人B-抗体调控下的VMPC11-C57BL/6-IgG2ab CH3蛋白 肌动蛋白启动子在各种不同类型的Ia+APC系中的表达 检测不同类型Ia+合成的内源性IgG2a APC将刺激IgH-1b特异性T细胞。总的来说，这些 实验将有望使我们更清楚地了解 抗原提呈细胞在MHC限制性T细胞中的可能作用 自身免疫球蛋白的识别及其在T细胞中的作用 细胞耐受性。

The broad objective of this research is to investigate T cell responses to self and nonself immunoglobulins. The fact that IgG2a antigens are naturally expressed in Ia B lymphoma cells known to be fully capable of antigen presentation and that the structure of the antigen is readily manipulated using recombinant DNA techniques gives this system unique advantages for studying possible relationships between complex intracellular trafficking pathways and MHC restriction specificity. We plan to construct pSV2gt vectors encoding various forms of the C57BL/6 IgG2ab CH3. We are particularly interested in this portion of the molecule because allotypic determinants recognized by Igh-1b-specific T cell are located in the CH3 domain. Soluble, membrane-bound,and cytoplasmic form(s) of the C57BL/6 IgG2ab CH3 will be expressed in transfected B lymphoma cell lines. We will characterize the protein products that are synthesized and test whether these molecules are presented to Class II-restricted T cells. A major goal is to determine whether endogenously synthesized IgG2a antigens become associated with Class II molecules intracellularly. We will also express the VMPC11 -C57BL/6 IgG2ab CH3 protein under control of the human B- actin promoter in a variety of different types of Ia+ APC lines to test whether endogenous IgG2a synthesized by different types of Ia+ APC will stimulate Igh-1b-specific T cells. Overall, these experiments will hopefully lead to a clearer understanding of the possible role of antigen-presenting cells in MHC-restricted T cell recognition of self immunoglobulins and processes involved in T cell tolerance.