T CELL GLYCOPROTEINS CONTROLLED BY IMMUNE RESPONSE GENES

高度调控的脊椎动物免疫系统保护动物免受 传染病和肿瘤疾病。监管失误可能会导致 肿瘤、传染病、免疫缺陷或自身免疫性疾病。免疫 反应(Ir)基因调节免疫，并定位在一个保存的簇中 在脊椎动物的进化过程中。IR基因产品为II类 蛋白质。辅助性和抑制性T细胞区分异源抗原 (非自体)和II类蛋白(自体)。 我们和其他人发现了ir基因控制的小鼠T细胞蛋白。国际空间站 基因关联强烈表明在免疫调节中发挥了作用。一 I-J蛋白存在于抑制性T细胞上。另一个，i-at，发生在 辅助性T细胞。I-J结构基因不在小鼠17号染色体上 IR基因簇。我们发现了4号染色体JT基因座控制着 I-J蛋白。这是否是结构基因还不得而知。抗体 TO I-J蛋白似乎阻断了T细胞的识别结构。 识别第II类蛋白的T细胞受体尚不清楚。 据推测，它可能由ir基因控制，但可能是编码的。 其他地方。IR基因相关的T细胞蛋白可能是II类蛋白 感受器。为了研究它们在识别和免疫调节中的作用，我们 计划对IR基因相关的T细胞蛋白进行遗传学和 在功能上。在流式细胞仪分析中使用特定的抗体，我们 将重新检查I-J等位基因株，分析I-JB基因控制，检测 等位基因排除，定位I-J结构基因，并测试在一个 回交。 细胞融合和基因转染将决定是否 I-J控制基因H-2和JT在同一细胞中必须是活性的。 分析嵌合T细胞将测试这些基因是否在 不同的细胞。我们将调查JT基因座是否发挥其作用 通过影响第II类蛋白的表达进行控制。我们将研究一个 可能与7号染色体有关。测定I-at蛋白的含量 基因控制将扩大我们的分析范围。最后，我们将探讨 IR基因相关T细胞蛋白的功能验证假设 它们是T细胞受体的第II类蛋白识别元件。

The highly-regulated vertebrate immune system protects animals from infectious and neoplastic diseases. Regulatory failures may result in neoplasia, infectious disease, immunodeficiency, or autoimmunity. Immune response (Ir) genes regulate immunity, and map in a cluster preserved throughout vertebrate evolution. Ir gene products are the class II proteins. Helper and suppressor T cells distinguish foreign antigen (nonself) and class II proteins (self) on other cells. We and others discovered Ir gene-controlled mouse T cell proteins. The Ir gene association strongly suggests a role in immunoregulation. One protein, I-J, occurs on suppressor T cells. Another, I-At, occurs on helper T cells. The I-J structural gene is not in the mouse chromosome 17 Ir gene cluster. We discovered the chromosome 4 Jt locus controlling the I-J protein. Whether this is the structural gene is unknown. Antibodies to I-J protein seem to block the T cell's recognition structure. The T cell receptor which recognizes class II proteins is unknown. Presumably, it would be controlled by Ir genes, but might be encoded elsewhere. The Ir-gene-associated T cell proteins may be class II protein receptors. To study their role in recognition and immunoregulation, we plan to characterize the Ir-gene-associated T cell proteins genetically and functionally. Using specific antibodies in a flow cytometric assay, we will re-examine I-J allelic strains, analyze I-Jb genetic control, test for allelic exclusion, map the I-J structural gene, and test linkages in a backcross. Cell fusions and gene transfection will determine whether the I-J-controlling genes H-2 and Jt must be active in the same cell. Analyzing chimeric T cells will test whether the genes are active in different cells. We will investigate whether the Jt locus exerts its control by influencing class II protein expression. We will study a possible chromosome 7 locus involvement. Determining the I-At protein's genetic control will extend our analysis. Finally, we will probe the function of Ir-gene-associated T cell proteins testing the hypothesis that these serve as the T cell receptor's class II protein recognition element.