ROLE OF IDIOTYPES IN THE IMMUNE SYSTEM

建议的项目涉及分子结构和在 免疫系统。单个杂交瘤产物(HP)，表达主要 A品系熊鼠抗苯丙氨酸(Ar)抗体的独特型 独特的独特型决定因素，在其他惠普测试中没有发现，但存在于 A株免疫血清。我们将研究一些这样的个体发育 决定因素以获得关于是否出现 特定的克隆类型是遗传编程的。在合作研究中，我们 将决定在早期免疫过程中是否出现自身抗id抗体 对AR半抗原的反应(如TNP的情况)，并干扰斑块 编队。使用定义明确的独特型系统应该有助于新的 了解这一监管体系的方法。我们将尝试 确定是否形成调节性T细胞以响应私人独特型 决定因素；调节性T细胞是否形成对 独特型决定因素；即独特型监管是否仅限于 主要的白痴类型。实验将用独特型共轭的 针对私人决定簇的抗独特型抗体的同基因细胞。 效应器T细胞谱系的范围将通过确定 这种私人独特型决定因素是否存在于T细胞上 治疗迟发性超敏反应。已知独特型特异性辅助T 细胞是主要独特型大量表达所必需的。我们会 确定这样的辅助细胞是否也需要表达次要基因 独特型。这解决了抗独特型药物的必要性这一普遍问题 帮助表达各种克隆型。其他人对…的影响的工作 抑制B细胞瘤分泌抗体的T细胞将被延长 使用具有独特型和抗独特型受体的T细胞。我们会作出努力 使FAB片断结晶，用于结晶学，许多反Ar 携带主要独特型的惠普公司。我们将提供杂交瘤用于 研究控制T细胞受体的基因，并将尝试获得 用于这些实验的连续T细胞系。

The projects proposed relate to molecular structures and regulation in the immune system. Individual hybridoma products (HP's), expressing the major idiotype of anti-phenylarsonate (anti-Ar) antibodies of strain A mice, bear unique idiotypic determinants, not found on other HP's tested but present in strain A immune serum. We will study the ontogeny of a number of such determinants to obtain additional information as to whether the appearance of particular clonotypes is genetically programmed. In collaborative research we will determine whether auto-anti-id antibodies appear during the early immune response to the Ar hapten (as is the case for TNP), and interfere with plaque formations. The use of a well-defined idiotypic system should facilitate new approaches toward understanding this regulatory system. We will attempt to determine whether regulatory T cells are formed in response to private idiotypic determinants; whether regulatory T cells are formed in response to private idiotypic determinants; i.e. whether idiotypic regulation is restricted to the major idiotypes. The experiments will be done by using idiotype-conjugated syngeneic cells for anti-idiotypic antibodies specific for private determinants. The extent of the effector T cell repertoire will be explored by determining whether such private idiotypic determinants are present on T cells responsible for delayed-type hypersensitivity. It is known that idiotype-specific helper T cells are required for substantial expression of the major idiotype. We will ascertain whether such helper cells are also needed for expression of a minor idiotype. This addresses the general question of the need for antiidiotypic help in the expression of various clonotypes. Work of others on the effects of suppressor T cells on secretion of antibody by B cell tumors will be extended by using T cells with idiotypic and antiidiotypic receptors. Efforts will be made to crystallize Fab fragments, for use in crystallography, of a number of anti-Ar HP's that carry the major idiotype. We will provide hybridomas to be used in a study of the genes controlling the T cell receptor and will attempt to obtain continuous T cell lines for use in those experiments.