Di Palma Francesco, Tramontano Anna
Department of Physics, Sapienza - Università di Roma, Italy.
Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Roma, Italy.
FEBS Lett. 2017 Sep;591(18):2936-2950. doi: 10.1002/1873-3468.12774. Epub 2017 Aug 30.
The investigation of antibody affinity maturation and its effects on antigen binding is important with respect to understanding the regulation of the immune response. To shed light on this crucial process, we analyzed two Igs neutralizing the human cytomegalovirus: the primary germline antibody M2J1 and its related mature antibody 8F9. Both antibodies target the AD-2S1 epitope of the gB envelope protein and are considered to establish similar interactions with the cognate antigen. We used molecular dynamics simulations to understand the effect of mutations on the antibody-antigen interactions. The results provide a qualitative explanation for the increased 8F9 peptide affinity compared with that of M2J1. The emerging atomistic-detailed description of these complexes reveals the molecular effects of the somatic hypermutations occurring during affinity maturation.
研究抗体亲和力成熟及其对抗原结合的影响对于理解免疫反应的调节至关重要。为了阐明这一关键过程，我们分析了两种中和人巨细胞病毒的免疫球蛋白：初级胚系抗体M2J1及其相关的成熟抗体8F9。这两种抗体均靶向gB包膜蛋白的AD-2S1表位，并被认为与同源抗原建立相似的相互作用。我们使用分子动力学模拟来理解突变对抗体-抗原相互作用的影响。结果为8F9肽与M2J1相比亲和力增加提供了定性解释。这些复合物新出现的原子水平详细描述揭示了亲和力成熟过程中发生的体细胞超突变的分子效应。
