Lehner T, Ma J K, Kelly C G
Department of Immunology, United Medical School, Guy's Hospital, London, United Kingdom.
Adv Exp Med Biol. 1992;327:151-63. doi: 10.1007/978-1-4615-3410-5_17.
The cell surface streptococcal antigen (SA) I/II of 185,000 M(r) is an immunodominant molecule that expresses one or more adhesion determinants. A series of 14 monoclonal antibodies (MAb) to defined parts of SA I/II were generated and some of these were used in passive immunization of macaques. Topical administration of selected MAb to the teeth of macaques prevented colonization of endogenous or implanted exogenous Streptococcus mutans for a period of 1 year. Significant reduction of both smooth surface and fissure caries was found in macaques who had MAb (Guy's 1) applied to their teeth, as compared with saline-treated animals. A series of in vivo passive immunization experiments was then carried out in 57 human subjects. Topical application of MAb to SA I/II prevented colonization of both artificially implanted exogenous strains of S. mutans, as well as natural recolonization by indigenous S. mutans. The properties of the protective MAb were then investigated and the epitope specificity within the SA I/II molecule was found to be essential but not the isotype specificity of the immunoglobulin (Ig). The requirement for complement activating and the phagocyte binding sites of the Fc fragment of MAb was not essential, as the F(ab')2 fragment of the MAb was as protective as the intact IgG, but the Fab fragment failed to prevent recolonization of S. mutans. Prevention of recolonization was specifically restricted to S. mutans, as the proportion of other organisms, such as S. sanguis, failed to show a significant change. The surprising feature of these experiments was that protection of re-colonization of S. mutans lasted up to 2 years, although MAb was applied for only 3 weeks and functional MAb was detected on the teeth only 3 days following application of the MAb. The long-term protection could therefore not be accounted for by a persistence of MAb on the teeth, but may be due to a shift in the microbial balance in which other bacteria occupy the ecological niche vacated by S. mutans, resulting in colonization resistance to S. mutans. Gene cloning and sequencing the SA from S. mutans, S. sobrinus and S. sanguis identified a conserved region (residues 955-1213) which on Southern hybridization and partial DNA sequence analysis was also found in 19 alpha-haemolytic oral streptococci. The results suggest that the SA molecule may constitute a family of adhesins in oral alpha haemolytic streptococci.(ABSTRACT TRUNCATED AT 400 WORDS)
分子量为185,000的细胞表面链球菌抗原（SA）I/II是一种免疫显性分子，表达一种或多种黏附决定簇。针对SA I/II特定部位产生了一系列14种单克隆抗体（MAb），其中一些用于猕猴的被动免疫。将选定的MAb局部应用于猕猴牙齿，可在1年内防止内源性或植入的外源性变形链球菌定植。与用盐水处理的动物相比，牙齿应用了MAb（盖伊氏1号）的猕猴，其平滑表面和窝沟龋均显著减少。随后在57名人类受试者中进行了一系列体内被动免疫实验。将MAb局部应用于SA I/II可防止人工植入的外源性变形链球菌菌株定植，以及内源性变形链球菌的自然再定植。然后研究了保护性MAb的特性，发现SA I/II分子内的表位特异性至关重要，而不是免疫球蛋白（Ig）的同种型特异性。MAb的Fc片段对补体激活和吞噬细胞结合位点的需求并非必需，因为MAb的F(ab')2片段与完整IgG一样具有保护作用，但Fab片段未能防止变形链球菌再定植。再定植的预防特异性地局限于变形链球菌，因为其他生物体（如血链球菌）的比例未显示出显著变化。这些实验令人惊讶的特点是，尽管MAb仅应用3周，且在应用MAb后仅3天在牙齿上检测到功能性MAb，但对变形链球菌再定植的保护持续长达2年。因此，长期保护不能用MAb在牙齿上的持续存在来解释，而可能是由于微生物平衡的改变，其中其他细菌占据了变形链球菌腾出的生态位，从而导致对变形链球菌的定植抗性。对变形链球菌、远缘链球菌和血链球菌的SA进行基因克隆和测序，确定了一个保守区域（第955 - 1213位氨基酸），在Southern杂交和部分DNA序列分析中，该区域在19种α - 溶血性口腔链球菌中也被发现。结果表明，SA分子可能构成口腔α - 溶血性链球菌中的一类黏附素家族。（摘要截断于400字）
