STRUCTURE AND EXPRESSION OF SUPPRESSOR T CELL PRODUCTS

T细胞对免疫系统的发育和调节是绝对必要的。 免疫反应，从而维持健康。 我们 了解T细胞亚群的多样性和生物活性， 广泛;然而，对T细胞的结构知之甚少 受体和T细胞介质。 本提案的目标是 分离、纯化和表征抗原特异性因子和受体 由各种抑制性T细胞亚群表达。 我们的战略 小鼠抑制性T细胞产物的分析是开发T细胞 通过筛选与抑制子类似的抑制子活性的杂交瘤 正常的T细胞。 我们已经制造了一个大的T细胞群， 杂交瘤很可能含有至少四种不同T细胞 子集 这些杂交瘤产生的因子具有抗原结合位点 并带有由H-2基因复合体编码的决定簇。 六架不同的H-2 单倍型表示在该图中。 我们建议刻画T 使用功能性血清学， 免疫化学和生物化学技术。 我们的具体目标是 确定原型抑制基因的结构和氨基酸序列 我们将其纯化为同质性。 所选T 细胞杂交瘤产物将揭示结构同源性的程度 在一个紧密相关的分子家族的成员之间。 我们将开发 用T细胞杂交瘤免疫或纯化的新血清学试剂 杂交瘤产物。 这些血清和单克隆抗体将用于 鉴定新I区基因产物并验证因子， 由T细胞杂交瘤产生的受体由类似的、正常的 体内调节性T细胞。 这些研究最终将导致 鉴定所有必需的、相互作用的T细胞亚群， 抗原特异性抑制途径。 此外，关于 参与抑制性T细胞活性的基因的数量和性质可以 使用这些抑制性T细胞杂交瘤来接近。

T cells are absolutely essential to the development and regulation of immune responses and consequently to the maintenance of health. Our knowledge of the diversity and biological activity of T cell subsets is extensive; yet, very little is known about the structure of T cell receptors and T cell mediators. The objectives of this proposal are to isolate, purify, and characterize antigen-specific factors and receptors expressed by various subsets of suppressor T cells. Our strategy for the analysis of murine suppressor T cell products was to develop T cell hybridomas by screening for suppressor activities analogous to suppressor activities of normal T cells. We have produced a large panel of T cell hybridomas that very likely contains a minimum of four distinctive T cell subsets. Factors produced by these hybridomas have antigen-binding sites and bear determinants encoded by the H-2 gene complex. Six different H-2 haplotypes are represented in this panel. We propose to characterize T cell products from these hybridomas using functional serological, immunochemical and biochemical techniques. Our specific aims are to determine the structure and amino acid sequence of a prototype suppressor factor which we have purified to homogeneity. Comparisons among selected T cell hybridoma products will reveal the degree of structural homology between members of a family of closely related molecules. We will develop new serological reagents by immunization with T cell hybridomas or purified hybridoma products. These sera and mono-lonal antibodies will be used to identify new I-region gene products and to verify that factors and receptors produced by T cell hybridomas are expressed by analogous, normal regulatory T cells in vivo. These studies should eventually lead to the identification of all essential, interacting T cell subsets in one antigen-specific suppressor pathway. In addition, questions concerning the number and nature of the genes involved in suppressor T cell activity can be approached using these suppressor T cell hybridomas.