STRUCTURE OF IDIOTYPE-ANTI-IDIOTYPE INTERACTIONS

抗原决定簇的化学基础及其 免疫应答中特异性抗体分子的识别 已经在许多研究中使用免疫学和 物理化学技术 尽管进行了大量的研究 活动，有几个问题仍然没有答案，例如 关于抗原决定簇的构象 （连续的或地形的），结构变化的影响 (such作为氨基酸替代物）对它们被特异性 抗体，和构象变化的性质， 免疫复合物形成后的抗原。 同样有趣的是 关于抗体作用的结构基础的问题，例如 由于抗原识别位点的物理范围， 抗体分子中发生的构象变化 免疫复合物形成后， 产生特异性和稳定性的化学键 这些情结。 抗原抗体相互作用的一个特例 是指抗原决定簇是 抗体，并且其中抗独特位抗体模拟 抗原，从而提供该抗原的“内部图像”。 独特型/抗独特型相互作用构成了 免疫系统的假定调节机制。 的 通过抗独特位抗体模拟外来抗原， 作为针对不同抗原的免疫的基础， 实际应用 为了研究上述问题，本实验室 利用细胞杂交技术， 针对鸡蛋清溶菌酶的抗体。 这种蛋白质 作为抗原选择，因为它的良好特征的三个- 三维结构、免疫原性和可用性。 在 此外，还提供了特异性抗溶菌酶抗体D1：3， 识别明确的抗原决定簇已被用于 获得抗独特型抗体，以及这些抗体之间的复合物 抗体和D1.3已经进行结晶试验。 因此获得了结晶复合物，并将 进行X射线衍射研究。 这些研究应 提供与结合位点相关的结构定义 idiotope和应该能够比较的三维 抗独特型抗体的结构与外部的结构 抗原的

The chemical bases of antigenic determinants and of their recognition by specific antibody molecules in immune responses have been explored in numerous studies using immunological and physiochemical techniques. In spite of this intense research activity, several questions remain unanswered, such as those concerning the conformation of antigenic determinants (continuous or topographical), the effect of structural changes (such as amino acid replacements) on their recognition by specific antibodies, and the nature of conformational changes in the antigen after immune complex formation. Equally interesting are questions concerning the structural bases of antibody action, such as the physical extent of the antigen recognition sites, the nature of conformational changes taking place in the antibody molecule after the formation of immune complexes and the nature of the chemical bonds that give rise to the specificity and stability of those complexes. A special case of antigen-antibody interactions is that in which the antigenic determinant is the idiotope of an antibody and in which the anti-idiotope antibody mimics the antigen, thus providing an "internal image" of that antigen. Idiotype/anti-idiotype interactions constitute the bases for postulated regulatory mechanisms of the immune system. The mimicking of foreign antigens by anti-idiotope antibodies has been as the basis for immunization against diverse antigens, a possible practical application. In order to study the problems outlined above this laboratory has used the technique of cellular hybridization to obtain monoclonal antibodies directed against hen egg-white lysozyme. This protein as chosen as the antigen because of its well characterized three- dimensional structure, immunogenicity and availability. In addition, a specific anti-lysozyme antibody, D1:3, which recognizes a well defined antigenic determinant has been used to obtain anti-idiotopic antibodies, and complexes between these antibodies and D1.3 have been submitted to crystallization trials. A crystalline complex has thus been obtained and will be submitted to X-ray diffraction studies. These studies should provide the structural definition of a combining-site related idiotope and should enable to compare the three-dimensional structure of the anti-idiotopic antibody with that of the external antigen.