2021年9月2日 · Fusion of the C-terminal tailpiece of IgM promoted spontaneous hIgG hexamer formation, resulting in enhanced C1q recruitment and complement-dependent cytotoxicity (CDC) but with off-target...

2014年3月14日 · We found that specific noncovalent interactions between Fc segments of immunoglobulin G (IgG) antibodies resulted in the formation of ordered antibody hexamers after antigen binding on cells. These hexamers recruited and activated C1, the first component of complement, thereby triggering the complement cascade.

2022年6月1日 · In this work, we assessed the colloidal, conformational, and long-term stability of IgG model compounds with stepwise increasing hexamer formation propensity. The chosen IgG model compounds were based on the HexaBody technology for which self-association was driven by the stabilization of interactions at a well-characterized Fc-Fc interface 35 ...

2016年7月7日 · Through certain mutations, Wang et al. stabilize IgG hexamers and demonstrate, by native mass spectrometry, how they bind efficiently to C1q/C1. Molecular features of these IgG hexamers, such as glycosylation, are assessed for their specific role in complement activation.

IgM C 末端尾片的融合促进了 hIgG 六聚体的自发形成，从而增强了 C1q 募集和补体依赖性细胞毒性 (CDC)，但会导致补体激活脱靶并降低体内功效。 倒数第二个尾段半胱氨酸突变为丝氨酸（C575S）消除了自发六聚体形成，但在溶液浓缩后促进了可逆六聚体形成。 C575S 突变尾片抗体仅在靶点结合后才表现出补体活性增加，符合“靶向六聚化”的概念，同时保留有效的体内功效并增强淋巴结中的靶细胞杀伤力。 因此，C575S-tailpiece 技术代表了促进目标六聚化和增强 …

2024年10月4日 · Combining hexamer-enhancing mutations has been shown to increase the propensity of IgG molecules to form hexamers in solution, as double mutants (e.g., E345R/E430G) produce a population of 7%–13% preformed hexamer and triple mutants (e.g., E345R/E430G/S440Y) produce a population of 50%–80% preformed hexamer. 49, …

2021年9月2日 · Herein is described an approach to exploit the tailpiece of the naturally multimeric IgM to augment hexamerisation of IgG. Fusion of the C-terminal tailpiece of IgM promoted spontaneous hIgG hexamer formation, resulting in enhanced C1q recruitment and complement-dependent cytotoxicity (CDC) but with off-target complement activation and reduced ...

2024年6月4日 · In this issue of the JCI, Cleary and colleagues utilized several approaches to demonstrate that IgG forms hexamers with MHC class I alloantibodies. This hexamerization served as a key pathophysiological mechanism in alloimmune lung injury models and was mediated through the classical pathway of complement activation.

2015年5月1日 · Specifically, identification of IgG Fc mutations designed to enhance hexamer formation could pave the way for the engineering of reagents that more effectively deplete their target populations, potentially facilitating the design of better T cell– or B cell–depleting agents for use in transplantation.

We found that specific noncovalent interactions between Fc segments of immunoglobulin G (IgG) antibodies resulted in the formation of ordered antibody hexamers after antigen binding on cells. These hexamers recruited and activated C1, the first component of complement, thereby triggering the complement cascade.