Brard F, Petit S, Coquerel G, Gilbert D, Koutouzov S, Perez G, Tron F
Groupe de Recherche en Immunopathologie, (IFR 23), Faculté Mixte de Médecine et de Pharmacie, Hôpital Charles Nicolle, Rouen, France.
Mol Immunol. 1997 Aug;34(11):793-807. doi: 10.1016/s0161-5890(97)00059-x.
Three-dimensional structural models of six murine anti-(H2A-H2B) monoclonal autoantibody variable fragments were built by comparative molecular modeling using the COMPOSER software. Analysis of the antibody combining sites is based on the hypothesis that ionic and/or electrostatic interactions predominate in antigen antibody binding, as suggested by the cationic nature of histones and the amino acid sequences of the antibody hypervariable regions. The study of the electrostatic potentials of their combining site surfaces, computed with the MOLCAD software, and the comparison with the electrostatic potentials of 13 selected control mAbs show the lack of a unique electrostatic pattern. One group of three mAbs expresses a strong and large electronegative area, supporting the hypothesis that ionic interactions predominate in antigen recognition. The second group, containing the other three mAbs, exhibits an alternation of electropositive and electronegative areas. All, however, present a localized electronegative area in the vicinity of H-CDR1 and H-CDR2 loops that is generated by the presence of at least one acidic residue. The model suggesting that the binding activity may depend on charged residues at the same site is reminiscent of what was previously reported in anti-DNA mAbs. In addition, the alternation of electropositive areas and electronegative areas in second group mAbs is also frequently observed in certain anti-DNA mAbs. These data argue for the existence of relationships between these two autoantibody populations and suggest that they share a common immunogenic particle formed by anionic and cationic components, such as a nucleosome.
使用COMPOSER软件通过比较分子建模构建了六种鼠抗（H2A - H2B）单克隆自身抗体可变片段的三维结构模型。抗体结合位点的分析基于这样的假设：由于组蛋白的阳离子性质和抗体高变区的氨基酸序列，离子和/或静电相互作用在抗原抗体结合中占主导地位。用MOLCAD软件计算其结合位点表面的静电势，并与13种选定的对照单克隆抗体的静电势进行比较，结果显示缺乏独特的静电模式。一组三种单克隆抗体表现出一个强且大的电负性区域，支持离子相互作用在抗原识别中占主导地位的假设。第二组包含另外三种单克隆抗体，呈现出正电和负电区域的交替。然而，所有抗体在H - CDR1和H - CDR2环附近都存在一个局部电负性区域，这是由至少一个酸性残基的存在所产生的。该模型表明结合活性可能取决于同一位点的带电残基，这让人想起先前在抗DNA单克隆抗体中的报道。此外，在某些抗DNA单克隆抗体中也经常观察到第二组单克隆抗体中正电区域和负电区域的交替。这些数据支持这两种自身抗体群体之间存在关联，并表明它们共享由阴离子和阳离子成分形成的共同免疫原性颗粒，如核小体。
