Westerink M A, Giardina P C, Apicella M A, Kieber-Emmons T
Department of Medicine, Medical College of Ohio, Toledo 43699, USA.
Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):4021-5. doi: 10.1073/pnas.92.9.4021.
Sequence analysis of the variable regions of the heavy and light chains of the anti-idiotypic antibody 6F9, which mimics the meningococcal group C capsular polysaccharide (MCP), was performed. The immunogenic site on 6F9 responsible for inducing an anti-MCP antibody response was determined by means of sequence and computer model analysis of these data. Complementarity-determining region 3 (CDR3) was found to be unique in that the sequence tract YRY was exposed on the surface. A synthetic peptide spanning the CDR3 domain was synthesized and complexed to proteosomes (meningococcal group B outer membrane protein). Immunizations of BALB/c mice with the peptide-proteosome complex resulted in a significant anti-MCP antibody response. Immunized mice were protected against infection with a lethal dose of Neisseria meningitidis serogroup C.
对模拟C群脑膜炎球菌荚膜多糖(MCP)的抗独特型抗体6F9的重链和轻链可变区进行了序列分析。通过对这些数据的序列和计算机模型分析,确定了6F9上负责诱导抗MCP抗体反应的免疫原性位点。发现互补决定区3(CDR3)具有独特性,即序列片段YRY暴露于表面。合成了跨越CDR3结构域的合成肽,并使其与蛋白酶体(B群脑膜炎球菌外膜蛋白)复合。用肽-蛋白酶体复合物免疫BALB/c小鼠可产生显著的抗MCP抗体反应。免疫小鼠对致死剂量的C群脑膜炎奈瑟菌感染具有抵抗力。