Buenafe A C, Rittenberg M B
Department of Microbiology and Immunology, Oregon Health Sciences University, Portland 97201.
Immunology. 1991 Aug;73(4):398-406.
We have analysed the serum antibody response of BALB/c mice to the organophosphorus toxin soman coupled to the protein carrier keyhole limpet haemocyanin (So-KLH) and compared the specificity of the serum antibodies to that of hybridomas described previously. The relative inhibitory capacities of various soman analogues for serum antibodies correlated with those for the monoclonal antibodies. Our results also demonstrate that immune memory to this organophosphorus hapten is stable for greater than 1 year. Interestingly, maturation of the serum antibody response is accompanied by fine specificity changes resulting in increased binding to soman-protein conjugates but not in significant changes in binding to free hapten analogues of soman. This finding suggests that contributions made by the protein carrier or bridge structure, including those made by amino acid side chains involved in the linkage, may play a significant role in the maturation process of antibodies recognizing protein-coupled organophosphorus haptens such as So-KLH. Structurally related but charge-dissimilar organophosphate haptens such as nitrophenylphosphocholine were poorly recognized, even when conjugated to protein with the same diazophenyl linkage used to conjugate soman. This is consistent with maintenance of high specificity in the memory immune response to soman-coupled protein.
我们分析了BALB/c小鼠对与蛋白质载体钥孔血蓝蛋白偶联的有机磷毒素梭曼（So-KLH）的血清抗体反应，并将血清抗体的特异性与先前描述的杂交瘤的特异性进行了比较。各种梭曼类似物对血清抗体的相对抑制能力与对单克隆抗体的抑制能力相关。我们的结果还表明，对这种有机磷半抗原的免疫记忆在1年以上是稳定的。有趣的是，血清抗体反应的成熟伴随着精细的特异性变化，导致与梭曼-蛋白质偶联物的结合增加，但与梭曼游离半抗原类似物的结合没有显著变化。这一发现表明，蛋白质载体或桥结构的贡献，包括参与连接的氨基酸侧链的贡献，可能在识别蛋白质偶联有机磷半抗原（如So-KLH）的抗体成熟过程中发挥重要作用。结构相关但电荷不同的有机磷酸半抗原，如硝基苯基磷胆碱，即使与用于偶联梭曼的相同重氮苯基连接物与蛋白质偶联，也很难被识别。这与对梭曼偶联蛋白的记忆免疫反应中高特异性的维持是一致的。
