López-Requena Alejandro, Mateo de Acosta Cristina, Bestagno Marco, Vázquez Ana María, Pérez Rolando, Burrone Oscar R
Department of Antibody Engineering, Center of Molecular Immunology, P.O. Box 16040, Havana 11600, Cuba.
Mol Immunol. 2007 Apr;44(11):3070-5. doi: 10.1016/j.molimm.2007.01.020. Epub 2007 Mar 2.
The heavy chain of anti-N-glycolyl-ganglioside P3 mAb plays the main role in its binding properties. At least one hybrid idiotype consisting on the P3 VH and an unrelated VL domain retains antigen recognition. Moreover, the unusual immunogenic properties of P3 idiotype could be modified by single mutations of H-CDR residues. Here, we show that DNA gene gun immunization with the P3 VH combined with an unrelated VL domain or with itself (VH dimer, VHD) is enough for inducing anti-idiotypic antibodies, independently of antigen recognition by the resulting molecule. The scFv fragment of P3 mAb was also able to induce an anti-idiotypic response. For both the P3 and the P3 anti-idiotypic 1E10 mAbs, heavy chains dominate the induction of antibodies against the respective idiotypes.
抗N-糖基化神经节苷脂P3单克隆抗体的重链在其结合特性中起主要作用。至少一种由P3重链可变区(VH)和不相关的轻链可变区(VL)组成的杂合独特型保留了抗原识别能力。此外,P3独特型不寻常的免疫原性特性可通过重链互补决定区(H-CDR)残基的单突变来改变。在此,我们表明,用P3 VH与不相关的VL结构域或其自身(VH二聚体,VHD)进行DNA基因枪免疫足以诱导抗独特型抗体,而与所得分子的抗原识别无关。P3单克隆抗体的单链抗体片段(scFv)也能够诱导抗独特型反应。对于P3和P3抗独特型1E10单克隆抗体,重链在针对各自独特型的抗体诱导中起主导作用。