Curtis M A, Aduse-Opoku J, Slaney J M, Rangarajan M, Booth V, Cridland J, Shepherd P
Department of Oral Microbiology, Medical Research Council Molecular Pathogenesis Group, London, United Kingdom. M. A.
Infect Immun. 1996 Jul;64(7):2532-9. doi: 10.1128/iai.64.7.2532-2539.1996.
This study was performed to characterize the antigen(s) recognized by a panel of monoclonal antibodies (MAbs) produced to be specific for Porphyromonas gingivalis whole cells which we had previously shown to bind to epitopes recognized by sera from periodontitis patients. Preliminary data had suggested that the arginine-specific proteases of P. gingivalis (ArgI, ArgIA, and ArgIB) contained the antigenic determinants of four of these antibodies (MAbs 1A1, 2B/H9, 7D5, and 3B1). The location of the binding sites was examined with purified P. gingivalis enzymes and recombinant regions of the ArgI polyprotein expressed by subclones of the prpR1 gene in Escherichia coli XL-1 Blue cells. All four antibodies were reactive with protein determinants within the beta subunit, a hemagglutinin and/or adhesin component, of the ArgI dimer. MAb 1A1 strongly inhibited the agglutination of human erythrocytes by P. gingivalis W50 culture supernatant, suggesting that the binding site for this antibody contains residues which are critical for the interaction with the erythrocyte surface. The determinant for MAb 1A1 was examined further by construction of a set of truncated forms of the beta component expressed as fusion proteins with glutathione S-transferase at the N terminus. Analysis of these constructs mapped the binding site for MAb 1A1 to PrpRI residues G-907 to T-931, GVSPKVCKDV TVEGSNEFAP VQNLT. Western blot (immunoblot) analysis of P. gingivalis whole-cell proteins demonstrated that MAb 1A1 reacts with several proteins in the Mr range of 20,000 to 120,000. Furthermore, an oligonucleotide probe corresponding to the coding sequence for the region of the ArgI beta component containing the MAb 1A1 binding site hybridized to multiple bands on genomic digests of P. gingivalis DNA. These data indicate that the MAb 1A1 epitope may be a component of a binding domain common to multiple gene products of this organism and may thus represent a functionally important target of the host's specific immune response to P. gingivalis in periodontal disease.
本研究旨在鉴定一组针对牙龈卟啉单胞菌全细胞产生的单克隆抗体(MAb)所识别的抗原,我们之前已证明这些全细胞可与牙周炎患者血清识别的表位结合。初步数据表明,牙龈卟啉单胞菌的精氨酸特异性蛋白酶(ArgI、ArgIA和ArgIB)包含其中四种抗体(MAb 1A1、2B/H9、7D5和3B1)的抗原决定簇。利用纯化的牙龈卟啉单胞菌酶以及在大肠杆菌XL-1 Blue细胞中由prpR1基因亚克隆表达的ArgI多蛋白的重组区域,检测了结合位点的位置。所有四种抗体均与ArgI二聚体β亚基内的蛋白质决定簇发生反应,β亚基是一种血凝素和/或粘附素成分。MAb 1A1强烈抑制牙龈卟啉单胞菌W50培养上清液对人红细胞的凝集作用,这表明该抗体的结合位点包含与红细胞表面相互作用至关重要的残基。通过构建一组在N端与谷胱甘肽S-转移酶融合表达的β成分截短形式,进一步研究了MAb 1A1的决定簇。对这些构建体的分析将MAb 1A1的结合位点定位到PrpRI的G-907至T-931残基,即GVSPKVCKDV TVEGSNEFAP VQNLT。对牙龈卟啉单胞菌全细胞蛋白的蛋白质印迹(免疫印迹)分析表明,MAb 1A1与分子量在20,000至120,000范围内的几种蛋白发生反应。此外,与包含MAb 1A1结合位点的ArgIβ成分区域编码序列相对应的寡核苷酸探针与牙龈卟啉单胞菌DNA基因组消化产物上的多条带杂交。这些数据表明,MAb 1A1表位可能是该生物体多种基因产物共有的结合域的一个组成部分,因此可能代表宿主对牙周疾病中牙龈卟啉单胞菌特异性免疫反应的一个功能重要靶点。