Emara M G, Tout N L, Kaushik A, Lam J S
Department of Microbiology, University of Guelph, Ontario, Canada.
J Immunol. 1995 Oct 15;155(8):3912-21.
The molecular nature of the murine Ab response to Pseudomonas aeruginosa LPS was examined using a panel of 10 well-defined anti-LPS mAbs. Abs to P. aeruginosa LPS are encoded by diverse V-genes, with at least five VH and four V kappa gene families represented in these Abs. The Abs that bind to hydrophilic O-polysaccharide side chains of B-band LPS and A-band LPS are encoded by VH J558, SM7, and J606 gene families, while Abs to hydrophobic core and lipid A regions are encoded by X24, SM7, and Q52 gene families. All active JH and only two J kappa (J kappa 2 and J kappa 5) germ-line genes are utilized in the anti-LPS Abs examined. Four of six anti-P. aeruginosa mAbs used diversity genes of the DSP2 gene family. Interestingly, JH1 and JH2 use was observed in three mAbs that reacted with hydrophilic LPS epitopes (O-polysaccharide, A-band LPS), whereas JH3 and JH4 use was observed in three mAbs that bound to the more hydrophobic regions of LPS (core, lipid A). Point mutations were observed in framework and complementarity-determining regions (CDRs) of VH and VL genes, suggesting an Ag-driven maturation process in response to P. aeruginosa LPS. Mutations occurred in all heavy chain CDRs, as well as in CDR1 and CDR3 of the light chain, indicating an important role of these regions in binding to LPS. These data suggest that diverse VH and V kappa genes encode Abs to LPS from P. aeruginosa.
使用一组10种明确界定的抗脂多糖单克隆抗体，研究了小鼠对铜绿假单胞菌脂多糖的抗体反应的分子性质。针对铜绿假单胞菌脂多糖的抗体由多种V基因编码，这些抗体中至少代表了五个VH和四个Vκ基因家族。与B带脂多糖和亲水O-多糖侧链以及A带脂多糖结合的抗体由VH J558、SM7和J606基因家族编码，而针对疏水核心和脂质A区域的抗体由X24、SM7和Q52基因家族编码。在所检测的抗脂多糖抗体中，所有活性JH基因和仅两个Jκ（Jκ2和Jκ5）种系基因被利用。六种抗铜绿假单胞菌单克隆抗体中有四种使用了DSP2基因家族的多样性基因。有趣的是，在三种与亲水脂多糖表位（O-多糖、A带脂多糖）反应的单克隆抗体中观察到JH1和JH2的使用，而在三种与脂多糖更疏水区域（核心、脂质A）结合的单克隆抗体中观察到JH3和JH4的使用。在VH和VL基因的框架区和互补决定区（CDR）中观察到点突变，表明对铜绿假单胞菌脂多糖的反应是一个抗原驱动的成熟过程。突变发生在所有重链CDR以及轻链的CDR1和CDR3中，表明这些区域在与脂多糖结合中起重要作用。这些数据表明，多种VH和Vκ基因编码针对铜绿假单胞菌脂多糖的抗体。
