IDIOTYPE RECOGNIZING T-HELPER CELLS

我们建议研究辅助性T细胞的特异性、功能和控制 识别B细胞产生的独特型。选定的骨髓瘤和 杂交瘤抗PC抗体将作为TNP的载体 B细胞反应。识别这些PC独特型的T辅助细胞 结合抗体通过以下方式产生：a)PC结合独特型， B)低剂量抗独特型抗体或c)PC-血蓝蛋白。 有限数量的T细胞被转移到无血缘关系的受者 从受者的脾制备碎片培养物。这个 用TNP偶联的抗PC独特型和 用ELIAS或RIA测定抗TNP抗体的产生。自.以来 识别独特型辅助性T细胞是由 抗独特型启动或通过抗原暴露，细胞回路中 将对T Help的诱导进行研究。T抑制细胞和T细胞的作用 抗体将通过采用转移进行研究。其次，罚款 识别辅助性T细胞的独特型的特异性将由In决定 使用独特型变体体外抑制独特型识别， 抗独特型抗体和分离的H链和L链。单一独生体 识别T辅助细胞将由抗独特型单抗产生 抗体及其良好的特异性将使用T15变种进行分析 杂交瘤作为TNP抗原。尽管反TNP读数并不完全 模拟暴露于抗原后发生的事件，这种方法允许 美国研究独特型特异性T-B相互作用。初步调查结果 表明T辅助细胞识别T15上的共同决定因素 与PC部位有关的独特型。由于这些目标 独特位在不同的血清学独特型中是相同的，并且似乎 在进化过程中保持稳定，它们可能会起到专门的“调控”作用 在控制抗PC反应中的独特性。特别有趣 是对T细胞特异性可能变化的长期观察 老化，准备好的小鼠的细胞。最后，将尝试获得T 辅助细胞克隆并使用它们的因子来研究可能的限制 在T-B互动中。

We propose to study the specificity, function and control of T-helper cells which recognize idiotypes produced by B-cells. Selected myeloma and hybridoma anti-PC antibodies will be used as carriers in a TNP-specific B-cell response. T-helper cells recognizing the idiotypes of these PC binding antibodies are generated by priming with: a) PC binding idiotypes, b) low doses of anti-idiotypic antibodies or c) with PC-hemocyanin. Limiting numbers of T-cells are transferred to athymic syngeneic recipients and fragment cultures are prepared from the recipient spleens. The cultures are immunized with TNP-coupled anti-PC idiotypes and the production of anti-TNP antibodies is measured by ELIAS or RIA. Since the idiotype recognizing T helper cells are generated indirectly by anti-idiotype priming or by antigen exposure, the cellular circuits in the induction of T help will be studied. The role of T suppressor cells and antibodies will be investigated by adoptive transfers. Next, the fine specificity of idiotype recognizing helper T cells will be determined by in vitro inhibition of idiotype recognition using idiotype variants, anti-idiotype antibodies and isolated H and L chains. Single idiotope recognizing T helpers will be generated by monoclonal anti-idiotypic antibodies and their fine specificity will be analyzed using T15 variant hybridomas as TNP-antigens. Although the anti-TNP readout does not exactly mimic events which occur after exposure to antigen, this approach permits us to study idiotype-specific T-B interactions. Preliminary findings indicate that T helper cells recognize shared determinants on the T15 idiotype which are related to the site for PC. Since these target idiotopes are shared among serologically different idiotypes and appear to be stable during evolution they might function as specialized "Regulatory Idiotopes" in the control of the anti-PC response. Of particular interest is the long-term observation of possible changes in the specificity of T cells in aging, primed mice. Finally, attempts will be made to obtain T helper cell clones and to use their factors to study possible restriction in T-B interactions.