Brade L, Engel R, Christ W J, Rietschel E T
Department of Immunochemistry and Biochemical Microbiology, Center for Medicine and Biosciences, Research Center Borstel, Germany.
Infect Immun. 1997 Sep;65(9):3961-5. doi: 10.1128/iai.65.9.3961-3965.1997.
Lipid A monoclonal antibodies, which require for binding the presence of the bisphosphorylated D-glucosamine disaccharide lipid A backbone, were tested against synthetic lipid A precursor Ia and compound B 1047 by enzyme immunoassay. The last-named compound is a precursor Ia analog with a methoxy instead of a hydroxy group at C6' and was chosen to determine why these antibodies failed to recognize the bound lipid A present in lipopolysaccharide (LPS). Whereas all antibodies tested bound to precursor Ia, none of them bound to compound B 1047 or Escherichia coli Re LPS to a significant extent. Compared to the natural substituent at C6', i.e., 3-deoxy-D-manno-octulosonic acid (Kdo), the methoxy group is neither bulky nor charged. Thus, the data suggest that it is not hindrance by Kdo but rather the generation of a neoantigen that endows lipid A with immunoreactivity upon liberation from LPS by acid hydrolysis.
脂质A单克隆抗体需要双磷酸化的D-葡糖胺二糖脂质A主链才能结合,通过酶免疫测定法对合成脂质A前体Ia和化合物B 1047进行了测试。后一种化合物是前体Ia类似物,在C6'处有一个甲氧基而非羟基,选择它是为了确定为什么这些抗体无法识别脂多糖(LPS)中结合的脂质A。尽管所有测试的抗体都与前体Ia结合,但它们都没有与化合物B 1047或大肠杆菌Re LPS发生显著结合。与C6'处的天然取代基即3-脱氧-D-甘露糖辛酸(Kdo)相比,甲氧基既不庞大也不带电荷。因此,数据表明,赋予脂质A免疫反应性的不是Kdo的阻碍,而是在通过酸水解从LPS释放后产生了一种新抗原。