IMMUNOREGULATORY T CELL GLYCOPROTEINS: GENE CLONING

免疫保护动物免受传染病的侵袭。某些T淋巴细胞 以高度选择性的方式调节免疫力。这些细胞区别于 来自外来抗原的自身组织。基因编码的膜糖蛋白 在小鼠中，称为H-2的簇出现在辅助细胞和B淋巴细胞上 调节性T细胞与之相互作用。这些糖蛋白参与了 在使外来抗原具有免疫原性的过程中，以及 从而影响调节性T细胞的诱导。 免疫调节的分子基础尚不完全清楚。 分离和鉴定重要的免疫调节分子具有 事实证明这很难。另一种方法是分离相关基因 通过基因克隆来调节免疫。由这些基因编码的蛋白质 然后可以获得足够的数量来允许生化反应 表征和生物学调查。 这项提议的具体目标是克隆编码两种基因的 重要的T淋巴细胞膜糖蛋白。两种糖蛋白都没有 是从T细胞中分离出来的，并进行了生化鉴定。一，I-J 糖蛋白，划分负责的抑制性T淋巴细胞类别 因为妨碍豁免权。另一种是I-at糖蛋白，它的特征是 增加负责增强免疫力的T淋巴细胞类别。这个 增强和抑制T淋巴细胞的调节活性是 对抗性。我们的初步结果表明，这两种糖蛋白 参与T细胞识别外来抗原的过程； 它们可能构成结合抗原的T细胞受体结构的一部分。 我们计划通过生产生物合成的细胞系来实现我们的目标 大量的I-J和I-AT糖蛋白。信使RNA 从细胞系中提取的DNA将作为合成cdna的模板； 将使用一种创新的方案克隆cDNA，该方案旨在促进 真核基因在细菌中的表达。翻译的蛋白质将是 通过免疫化学检测到。如果这个计划被证明是不合适的， 提出了可供选择的策略。

Immunity protects animals from infectious diseases. Certain T lymphocytes regulate immunity in a highly-selective manner. These cells distinguish self tissue from foreign antigen. Membrane glycoproteins encoded by a gene cluster termed H-2 in the mouse occur on accessory cells and B lymphocytes with which regulatory T cells interact. These glycoproteins are involved in the process by which foreign antigen is rendered immunogenic, and thereby influence regulatory T cell induction. The molecular basis for immune regulation is not completely understood. Isolating and characterizing important immunoregulatory molecules has proven difficult. An alternative approach is to isolate the genes involved in regulating immunity by gene cloning. Proteins encoded by these genes can then be obtained in sufficient quantity to permit biochemical characterization and biological investigation. The specific aim of this proposal is to clone the genes encoding two important T lymphocyte membrane glycoproteins. Neither glycoprotein has been isolated from T cells and characterized biochemically. One, the I-J glycoprotein, demarcates a suppressive class of T lymphocytes responsible for impeding immunity. The other, I-At glycoprotein, characterizes and augmenting class of T lymphocytes responsible for enhancing immunity. The regulating activities of augmenting and suppressive T lymphocytes are antagonistic. Our preliminary results suggest that both glycoproteins participate in the process by which T cells distinguish foreign antigen; they may form part of a T cell receptor structure that binds antigen. We plan to achieve our goal by producing cell lines that biosynthesize significant quantities of the I-J and I-At glycoproteins. Messenger RNA derived from the cell lines will serve as a template for cDNA synthesis; cDNA will be cloned using an innovative scheme designed to facilitate eukaryotic gene expression in bacteria. Translated proteins will be detected immunochemically. Should this scheme prove unsuitable, alternative strategies are proposed.