Ebersole J L, Bauman G R, Cox O'Dell S E, Giardino A
Department of Periodontics, University of Texas Health Science Center at San Antonio 78284, USA.
Oral Microbiol Immunol. 1997 Aug;12(4):193-203. doi: 10.1111/j.1399-302x.1997.tb00379.x.
This investigation determined the capacity of murine monoclonal antibodies directed to human immunoglobulin G (IgG) subclasses to identify molecules with conserved epitopes in the serum of the nonhuman primate, Macaca fascicularis. We subsequently utilized this cross-reactivity to document the characteristics of IgG subclass antibody responses in M. fascicularis to parenteral immunization with intact oral microorganisms, antigens from oral microorganisms, and finally a defined protein toxin, tetanus toxoid. The IgG response in nonhuman primates immunized with tetanus toxoid showed a 40-fold and 110-fold increase after primary and secondary immunizations, respectively. The major IgG subclass responses were IgG1 and IgG3, with little, though significant, responses in the IgG4 and IgG2 subclasses. Seventy-five to 94% of the natural IgG antibody in nonhuman primate sera to Porphyromonas gingivalis, Prevotella intermedia and Campylobacter rectus was IgG1. IgG2 and IgG3 predominated to Bacteroides fragilis, IgG4 to Actinomyces viscosus and an equal distribution among the subclasses was noted in response to Fusobacterium nucleatum. Parenteral immunization of nonhuman primates with intact P. gingivalis elicited primarily IgG3 and IgG4, while the post-immunization IgG response to P. intermedia was largely IgG1. Nonhuman primates were also parenterally immunized with cell envelope antigens of P. gingivalis, P. intermedia, or a combination of cell envelope antigen from C. rectus and F. nucleatum and cell wall antigens of A. viscosus. The greatest IgG antibody response seen post-immunization was reactive with anti-human IgG1 for all of these antigens except to C. rectus which bound nonhuman primate antibody reactive with anti-human IgG2. It appears that the bacteria and their products exhibit unique differences in their induction of serum IgG subclass antibody responses. The characteristics of their immunogenicity as detected by the nonhuman primate may contribute to the ability of the immune responses to effectively interact with these pathogens.
本研究确定了针对人免疫球蛋白G(IgG)亚类的鼠单克隆抗体识别食蟹猴血清中具有保守表位分子的能力。随后,我们利用这种交叉反应性来记录食蟹猴对完整口腔微生物、口腔微生物抗原以及最终一种特定蛋白毒素破伤风类毒素进行肠胃外免疫后IgG亚类抗体反应的特征。用破伤风类毒素免疫的非人灵长类动物的IgG反应在初次免疫和二次免疫后分别增加了40倍和110倍。主要的IgG亚类反应是IgG1和IgG3,IgG4和IgG2亚类反应虽小但有统计学意义。非人灵长类动物血清中针对牙龈卟啉单胞菌、中间普氏菌和直肠弯曲菌的天然IgG抗体,75%至94%为IgG1。针对脆弱拟杆菌,IgG2和IgG3占主导;针对粘性放线菌,IgG4占主导;针对具核梭杆菌的反应中,各亚类分布均等。用完整的牙龈卟啉单胞菌对非人灵长类动物进行肠胃外免疫主要引发IgG3和IgG4,而免疫后对中间普氏菌的IgG反应主要是IgG1。还用牙龈卟啉单胞菌、中间普氏菌的细胞壁抗原,或直肠弯曲菌的细胞壁抗原与具核梭杆菌的细胞壁抗原及粘性放线菌的细胞壁抗原的组合对非人灵长类动物进行肠胃外免疫。免疫后观察到的最大IgG抗体反应与抗人IgG1反应,除直肠弯曲菌外,所有这些抗原均如此,直肠弯曲菌结合与抗人IgG2反应的非人灵长类动物抗体。看来细菌及其产物在诱导血清IgG亚类抗体反应方面表现出独特差异。非人灵长类动物检测到的它们的免疫原性特征可能有助于免疫反应与这些病原体有效相互作用的能力。