Wang Xin-Min, Cook James C, Lee Jessica C, Jansen Kathrin U, Christensen Neil D, Ludmerer Steven W, McClements William L
Merck Research Laboratories, PO Box 4, West Point, PA 19486, USA.
The Jake Gittlen Cancer Research Institute, Department of Pathology, Penn State University, Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, USA.
J Gen Virol. 2003 Jun;84(Pt 6):1493-1497. doi: 10.1099/vir.0.18872-0.
The epitope for a human papillomavirus (HPV) type 6 conformation-dependent, neutralizing monoclonal antibody (mAb) was partially mapped using HPV L1 recombinant virus-like particles (VLPs). The mAb H6.J54 is cross-reactive with the closely related HPV types 6 and 11. By making HPV-6-like amino acid substitutions in the cottontail rabbit papillomavirus (CRPV) major capsid protein L1, we were able to transfer H6.J54 binding activity into a CRPV/HPV-6 hybrid L1 protein. Full binding activity was achieved with only nine amino acid changes and identified a region centred on the HPV-6 residues 49-54. This region has previously been shown to be a critical part of HPV-6 type-specific epitopes. Fine mapping of the region by scanning a series of alanine substitution mutations showed that in HPV-6 VLPs this type-common epitope overlaps HPV-6 type-specific epitopes.
利用人乳头瘤病毒(HPV)L1重组病毒样颗粒(VLPs)对人乳头瘤病毒6型(HPV-6)构象依赖性中和单克隆抗体(mAb)的表位进行了部分定位。单克隆抗体H6.J54与密切相关的HPV-6型和11型具有交叉反应性。通过在棉尾兔乳头瘤病毒(CRPV)主要衣壳蛋白L1中进行HPV-6样氨基酸替换,我们能够将H6.J54结合活性转移到CRPV/HPV-6杂交L1蛋白中。仅通过九个氨基酸的改变就实现了完全结合活性,并确定了一个以HPV-6第49-54位残基为中心的区域。该区域先前已被证明是HPV-6型特异性表位的关键部分。通过扫描一系列丙氨酸替代突变对该区域进行精细定位,结果表明在HPV-6 VLPs中,这种类型共同的表位与HPV-6型特异性表位重叠。