IMMUNOREGULATORY T CELL GLYCOPROTEINS: GENE CLONING

免疫力保护动物免受传染病的侵害。 某些T淋巴细胞 以高度选择性的方式调节免疫力。 这些细胞区分 自身组织与外来抗原的反应。 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 在使外源抗原具有免疫原性的过程中，和 从而影响调节性T细胞诱导。 免疫调节的分子基础还不完全清楚。 分离和表征重要的免疫调节分子， 证明困难。 另一种方法是分离相关基因 通过基因克隆来调节免疫力。 由这些基因编码的蛋白质 然后可以获得足够的量， 特征和生物学研究。 这项提议的具体目标是克隆编码两种 重要T淋巴细胞膜糖蛋白。 两种糖蛋白都没有 从T细胞中分离出来并进行了生物化学表征。 第一，I-J 糖蛋白，划分了一个抑制类的T淋巴细胞负责 因为妨碍了豁免权 另一种是I-At糖蛋白， 增强类T淋巴细胞负责增强免疫力。 的 增强和抑制T淋巴细胞的调节活性是 敌对 我们的初步结果表明，这两种糖蛋白 参与T细胞识别外源抗原的过程; 它们可以形成结合抗原的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 显著量的I-J和I-At糖蛋白。 信使RNA 来源于细胞系的DNA将用作cDNA合成的模板; cDNA将使用一种创新的方案进行克隆， 真核基因在细菌中的表达。 翻译的蛋白质将 免疫化学检测。 如果这个计划不合适， 提出了替代战略。

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.