IDIOTYPE RECOGNIZING T-HELPER CELLS

目的是研究独特型网络的发展在 老鼠的个体发育。我们工作的重点是T帮手的作用 识别BALB/c应答中主要T15独特型的细胞 小鼠对磷胆碱(PC)的作用。要检验的假设是， 在个体发病的早期，生殖系编码的B细胞独特型影响 调节性T细胞谱系。监管机构的拟议角色， 识别T细胞独特型是维持基本的B细胞谱系 维护正常运行的网络所必需的。 我们已经建立了测定独特型识别T的T帮助的方法 B细胞对独特型半抗原载体抗原的反应。我们 已经观察到T15特异性辅助细胞识别共同的独特位 这是由重链表示的。我们还定义了诱导性T细胞 它启动了独特型识别辅助细胞。它的独特性 诱导性T细胞是抗独特型的。该T-T细胞电路可以被触发 通过PC抗原，因此可能参与对细菌PC的反应 含有抗原的。 我们建议制备T细胞系、克隆和杂交瘤，它们是 独特型特有。我们将对这些细胞系进行测试，看它们是否 特异性、MHC限制和作为调节独特型的作用 体内和体外对PC的反应。确定的单抗独特型 生物活性将用于新生小鼠和 B细胞和T细胞对PC反应的网络变化 将对车厢进行分析。其中一个反白痴表达了 PC的内部镜像，即是Ab2Beta。T15的前兆频率 识别辅助性T细胞将被视为新生儿操纵 此外，还将分析独特型优良的特异性。一个 寻找T抑制细胞也将使用过继转移完成 我们实验室早些时候开发的协议。 最后，将制备转基因小鼠来研究独特型的影响 以及免疫网络个体发育上的抗独特型表达基因。 这种方法允许我们一次操纵免疫系统 在任何重排和对独特型表达承诺之前的个体发育 是由B细胞和T细胞组成的。我们预计这些独特型操作将 对网络的发展产生了深远的影响。我们将分析 这些变化通过关注T15/PC响应在两个T助手中 细胞室和B细胞室。

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.