Bruderer U, Stenzel-Poore M P, Bächinger H P, Fellman J H, Rittenberg M B
Department of Microbiology and Immunology, Oregon Health Sciences University, Portland 97201.
Mol Immunol. 1989 Jan;26(1):63-71. doi: 10.1016/0161-5890(89)90021-7.
The memory response to PC-KLH is dominated by two antibody populations differing in fine specificity. Group I antibodies show affinity for both phosphocholine (PC) and p-nitrophenyl phosphocholine (NPPC). Group II antibodies exhibit significant affinity only for NPPC. Here, we describe the binding site characteristics of Group II antibodies and show that in recognizing NPPC these antibodies have a common requirement for the phenyl moiety, a negatively charged phosphate, and the trimethyl structure of the choline. However, Group II antibodies were found to differ in their requirement for the positively charged nitrogen of choline and thus could be divided into two subgroups. In contrast to Group II-A, Group II-B antibodies recognize not only NPPC but also its analog p-nitrophenyl-3,3-dimethyl butyl phosphate (NPDBP), which differs from NPPC by substituting a carbon for the positively charged nitrogen of the choline moiety. These results suggest that Group II-B antibodies do not require the positive charge in order to bind, although the binding constant, Ka, was increased when the nitrogen was present. Furthermore, heterogeneity within Group II antibodies was characterized by differences in binding to dinitrophenyl phosphocholine which has an additional phenyl ring and aminophenyl phosphocholine which has an amino group in place of the nitro group of NPPC. The results indicate that diversity in the memory response to PC-KLH is reflected in the Group II antigen-binding phenotype by antibodies which differ appreciably in their recognition of various structural aspects of the hapten.
对磷酰胆碱-钥孔血蓝蛋白(PC-KLH)的记忆反应由两个精细特异性不同的抗体群体主导。第一组抗体对磷酰胆碱(PC)和对硝基苯基磷酰胆碱(NPPC)均有亲和力。第二组抗体仅对NPPC表现出显著亲和力。在此,我们描述了第二组抗体的结合位点特征,并表明在识别NPPC时,这些抗体对苯基部分、带负电荷的磷酸基团以及胆碱的三甲基结构有共同需求。然而,发现第二组抗体对胆碱带正电荷的氮的需求不同,因此可分为两个亚组。与II-A组不同,II-B组抗体不仅识别NPPC,还识别其类似物对硝基苯基-3,3-二甲基丁基磷酸酯(NPDBP),NPDBP与NPPC的区别在于用一个碳原子取代了胆碱部分带正电荷的氮。这些结果表明,II-B组抗体结合时不需要正电荷,尽管当氮存在时结合常数Ka会增加。此外,II组抗体的异质性表现为与二硝基苯基磷酰胆碱(有一个额外苯环)和氨基苯基磷酰胆碱(用氨基取代了NPPC的硝基)结合的差异。结果表明,对PC-KLH记忆反应的多样性在II组抗原结合表型中体现为抗体对半抗原不同结构方面的识别存在明显差异。