STRUCTURE OF IDIOTYPE-ANTI-IDIOTYPE INTERACTIONS

抗原决定簇及其决定簇的化学基础 免疫应答中特异性抗体分子的识别作用 在许多研究中都得到了探索，使用免疫学和 物理化学技术。尽管进行了密集的研究 活动中，有几个问题仍未得到回答，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 (如氨基酸替换)对它们的特定识别 抗体，以及构象变化的性质 免疫复合体形成后的抗原。同样有趣的是 关于抗体作用的结构基础的问题，如 由于抗原识别部位的物理范围，自然 抗体分子中发生的构象变化 免疫复合体形成后的性质和性质 化学键引起的特异性和稳定性 那些情结。抗原-抗体相互作用的一种特例 其中的抗原决定簇是一个独特位 抗体，其中抗独特位抗体模仿 抗原，从而提供该抗原的“内部图像”。 独特型/反独特型相互作用构成了 假定的免疫系统的调节机制。这个 用抗独特位抗体模拟外来抗原已被证实 作为针对不同抗原的免疫基础，可能的 实际应用。 为了研究以上概述的问题，本实验室 利用细胞杂交技术获得单克隆化 针对蛋清溶菌酶的抗体。这种蛋白质 被选为抗原是因为它有三个很好的特性- 维度结构、免疫原性和可用性。在……里面 另外，特异性抗溶菌酶抗体，D1：3， 识别一种定义明确的抗原决定簇已被用于 获得抗特异体抗体，以及它们之间的复合体 抗体和D1.3已提交结晶试验。 这样就得到了一种结晶的络合物，并将 提交给X射线衍射研究。这些研究应该 提供与合并站点相关的结构定义 独具特色和应该能够比较的三维 抗异位抗体与外源抗体的结构比较 抗原。

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.