IDIOTYPE RECOGNIZING T-HELPER CELLS

独特型识别 T 辅助细胞

• 批准号: 3115003
• 负责人: HEINZ KOHLER
• 金额: $ 13.51万
• 依托单位: IDEC PHARMACEUTICALS CORPORATION
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-05-01 至 1992-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3115003
• 关键词: B lymphocyte; animal age group; antibody specificity; athymic mouse; enzyme linked immunosorbent assay; haptens; helper T lymphocyte; hemocyanin; hybridomas; immunoglobulin genes; immunoglobulin idiotypes; laboratory mouse; major histocompatibility complex; monoclonal antibody; phosphorylcholine; radioimmunoassay; suppressor T lymphocyte

The objective is to study the development of the idiotype network during the ontogeny of mice. The focus in our work is on the role of T helper cells which recognize the dominant T15 idiotype in the response of BALB/c mice to phosphorylcholine (PC). The hypothesis to be tested states that early in ontogency, germ line encoded B cell idiotypes influences the repertoire of regulatory T cells. The proposed role of regulatory, idiotype recognizing T cells is to maintain a basic B cell repertoire necessary to preserve a functional network. We have established assays to measure T help of idiotype recognizing T cells for B cells responding to an idiotype hapten carrier antigen. We have observed that T15 specific helper cells recognize a shared idiotope which is expressed by the heavy chain. We also defined an inducer T cell which primes the idiotype recognizing helper cell. The specificity of the inducer T cells is anti-idiotypic. This T-T cell circuit can be triggered by PC antigen and may therefore be involved in the response to bacterial PC containing antigens. We propose to prepare T cell line, clones and hybridomas, which are idiotype specific. We will test these cell lines for their fine specificity, MHC restriction and role as regulatory idiotypes in the response to PC in vivo and in vitro. Monoclonal anti-idiotypes of defined biological activities will be administered to neonatal mice and the alteration of the network in the response to PC in the B and T cell compartments will be analyzed. One of the anti-idiotopes expresses the internal image of PC, i.e., is an Ab2Beta. The precursor frequency of T15 recognizing T helper cells will be followed as a neonatally manipulated mature mice; further, the idiotype fine specificity will be analyzed. A search for T suppressor cells will also be done using adoptive transfer protocols developed earlier in our lab. Finally, transgenic mice will be prepared to study the effect of idiotype and anti-idiotype expressing genes on the ontogeny of the immune network. This approach allows us to manipulate the immune system at a time in ontogeny before any rearrangements and committments to idiotype expression is made in B and T cells. We expect tha these idiotype manipulations will have profound effects on the development of the network. We will analyze these alterations by focusing on the T15/PC response in both the T helper cell and the B cell compartments.

本研究的目的是研究个体基因型网络的发展， 老鼠的个体发育 我们工作的重点是T辅助细胞的作用 识别BALB/c应答中显性T15独特型的细胞 磷酸胆碱（PC）。 有待检验的假设是， 在个体发育的早期，生殖系编码的B细胞独特型影响着 调节性T细胞库。 拟议的监管作用， 独特型识别T细胞是为了维持基本的B细胞库 保持一个功能网络的必要性。 我们已经建立了检测独特型识别T细胞的T辅助的方法， 对独特型半抗原载体抗原应答的B细胞。 我们 我观察到T15特异性辅助细胞识别一个共享的独特位， 其由重链表达。 我们还定义了一种诱导T细胞 启动独特型识别辅助细胞 的特异性 诱导T细胞是抗独特型的。 这个T细胞回路可以被触发 因此可能参与对细菌PC的应答 含有抗原。 我们建议制备T细胞系、克隆和杂交瘤，它们是 独特型特异性。 我们将测试这些细胞系的优良性能， 特异性、MHC限制性和作为调节独特型的作用， 在体内和体外对PC的反应。 单克隆抗独特型 生物活性将给予新生小鼠， B和T细胞中对PC应答的网络改变 将对隔间进行分析。 其中一个抗独特位表达 PC的内部映像，即，是Ab 2Beta T15的前兆频率 识别辅助性T细胞将作为一种神经操纵的 成熟小鼠;此外，将分析独特型精细特异性。 一 还将使用过继转移进行T抑制细胞的搜索 我们实验室早期开发的协议 最后，将制备转基因小鼠以研究独特型的影响。 和抗独特型表达基因对免疫网络的个体发育的影响。 这种方法使我们能够在一段时间内操纵免疫系统， 个体发育之前的任何重新安排和承诺独特型表达 是在B和T细胞中产生的。 我们希望这些独特型的操作 对网络的发展有着深远的影响。 我们将分析 通过关注T辅助细胞和T淋巴细胞中的T15/PC反应， 细胞和B细胞区室。