THE MECHANISM OF ANTIGEN-ANTIBODY INTERACTION

几种Fab片段-蛋白质抗原复合体的结构 其他人的X射线结晶学，揭示了基团接触的细节 在抗原-抗体界面上。然而，尽管有这样的解释， 相互作用基团、抗原结合相互作用和相互作用 其致病机制尚不十分清楚。 例如，疏水相互作用、氢键、 静电相互作用和范德华力被认为是足够的。 来描述抗原-抗体的相互作用。 在蛋白质折叠的研究中(见项目Z01DK25011-17LCB)，我们有 发展了一种新的非共价相互作用模型，即核心环 相互作用/核心环合并，推动折叠。这个核心环路 通过以下方式假设交互对群接触的细节敏感 其中的交互作用是通过媒介实现的。我们认为这样的核心环路 相互作用可能是抗原-抗体具有良好特异性的原因。 互动。如果这一假设是正确的，抗原与抗体结合 应稳定疏水核心远离抗原结合部位 抗体。为了验证这一假设，我们测量了酰胺氢 单克隆菌株4-128-6、4-74-6和2-96-12对酵母iso-1-1的交换率 细胞色素c在有无抗原的情况下。酰胺氢- 用红外分光光度法在Pd为7.0，24-时进行了氢交换。 摄氏25度。每摩尔增加约48摩尔和43摩尔的酰胺氢 单克隆4-128-6和4-74-6的抗原结合位点 在有抗原存在的情况下，48和72小时后保持不交换 马细胞色素c的存在。马细胞色素c不发生交叉反应 有了这些单克隆体。 单抗2-96-12的结果指向了一个新的方面：两者都 酵母iso-1和金枪鱼细胞色素c对 单抗对氢交换率的降低比马更大。 细胞色素c亲和力较低。这些观察表明， 从抗体的抗原结合部位移除的核心区域是 通过抗原结合来稳定。根据核心环路相互作用 理论上，VH和VL结构域的疏水核心可以 影响抗原-抗体相互作用。

The structures of several Fab fragment-protein antigen complexes, shown by X-ray crystallography by others, have revealed the details of group contact in the antigen-antibody interface. However, despite such elucidation of the interacting groups, the antigen binding-interaction and the interaction mechanism responsible for the fine specificity are not well understood. For example, a combination of hydrophobic interaction, hydrogen bonds, electrostatic interaction and Van der Waals force is considered sufficient to describe the antigen-antibody interaction. In the studies of protein folding (see Project Z01DK25011-17 LCB) we have developed a model of a new non-covalent interaction, namely core loop interaction/core loop coalescence which drives folding. This core loop interaction is assumed to be sensitive to the detail of group contact by which the interaction is mediated. We have thought that such core loop interaction may be responsible for the fine specificity of antigen-antibody interaction. If this hypothesis is correct, antigen binding to antibody should stabilize the hydrophobic cores far from the antigen-binding site of antibodies. To test this hypothesis, we have measured amide hydrogen exchange rates of monoclonals 4-128-6, 4-74-6 and 2-96-12 to yeast iso-1- cytochrome c in the presence and absence of antigen. The amide hydrogen- deuterium exchange was followed by infrared spectrophotometry at pD 7.0,24- 25oC. Approximately 48 and 43 more mol of amide hydrogens per mol of antigen binding site, respectively of monoclonals 4-128-6 and 4-74-6 remained unexchanged after 48 and 72 h in the presence of antigen than in the presence of horse cytochrome c. Horse cytochrome c does not crossreact with these monoclonals. The results with monoclonal 2-96-12 has pointed to a novel aspect: both yeast iso-1 and tuna cytochromes c which have higher affinity to the monoclonal have decreased the hydrogen exchange rate more than horse cytochrome c which has lower affinity. These observations indicate that the core regions removed from the antigen-binding site of antibodies are stabilized by antigen-binding. In light of the core loop interaction theory it follows that the hydrophobic cores of VH and VL domains may influence the antigen-antibody interaction.