CHARACTERISTICS OF T CELL RECEPTORS

该应用程序旨在研究T细胞的各种特性 受体。 我们将集中讨论那些识别抗原的受体 与主要组织相容性复合体（MHC）产物相关 （抗原/H-2）。 我们的最终目标是找出并隔离 负责这种识别的分子并绘制它们的图谱 遗传的 我们将在这些研究中得到很大的帮助， 我们实验室的技术发展，T细胞 识别抗原/H-2产物的杂交瘤。 这些杂交瘤 在正常组织培养基中连续快速地培养。 当面对 然而，在适当的抗原/H-2组合下，它们分泌 白细胞介素2。 它们还结合抗原脉冲呈递细胞， H-2单倍型。 将尝试描述 抗原/H-2受体免疫化学和生物化学。 免疫化学 分析将包括对抗血清和B杂交瘤的研究， T细胞杂交瘤，特别强调那些阻断 抗原结合 生化分析将包括尝试分离 抗原和/或H-2结合材料。 在 与Hood博士合作，我们将研究IG的表达 这些细胞中的重蛋白样mRNA。 磷酰胆碱（PC）反应性 将制备杂交瘤以检查VH基因和编码以下的mRNA的状态： PC结合重链。 在与Riblet博士的合作研究中，我们将 制备可用于重链、κ和λ分析的杂交体 基因重排 体细胞遗传学将用于确定 染色体编码抗原/H-2的T细胞受体。 T细胞 杂交瘤将使用抗原特异性亲代T细胞制备，其中 标记的染色体，以及保留或失去抗原的亚系 特异性特异性和标记的染色体的重合将 请注意。 此外，与Francke博士合作， 将分析已经存在的杂交瘤的非反应性变体， 染色体丢失

This application is designed to study various properties of T cell receptors. We will concentrate on those receptors which recognize antigen in association with major histocompatibility complex (MHC) products (antigen/H-2) in the mouse. Our ultimate goals are to identify and isolate the molecule(s) responsibile for this recognition and to map them genetically. We will be greatly helped in these studies by the recent development in our laboratory of techniques for preparing cloned ?T cell hybridomas which recognize antigen/H-2 products. These hybridomas grow continuously and rapidly in normal tissue culture medium. When confronted with the appropriate antigen/H-2 combination, however, they secrete interleukin-2. They also bind to antigen-pulsed presenting cells of the appropriate H-2 haplotype. Attempts will be made to characterize the antigen/H-2 receptor(s) immunochemically and biochemically. Immunochemical analysis will include studies on antisera and B hybridomas raised against the T cell hybridomas, with particular emphasis on those which block antigen binding. Biochemical analysis will include attempts to isolate antigen and/or H-2 binding material from radiolabelled cells. In collaboration with Dr. Hood we will investigate the expression of Ig heavy-like mRNA in these cells. Phosphoryl choline (PC)-reactive hybridomas will be made to check the status of VH genes and mRNA coding for PC-binding heavy chains. In collaborative studies with Dr. Riblet we will prepare hybrids which can be used for analysis of heavy, kappa and lambda gene rearrangements. Somatic cell genetics will be used to establish which chromosomes code for the T cell receptor(s) for antigen/H-2. T cell hybridomas will be prepared using antigen specific parental T cells with marked chromosomes, and in sublines which retain or have lost antigen specificity the coincidence of specificity and the marked chromosomes will be noted. In addition, in collaboration with Dr. Francke, antigen non-reactive variants of already existing hybridomas will be analyzed for chromosome loss.