免疫球蛋白G4 Fab-臂交换的机制
Theo Rispens1, Pleuni Ooijevaar-de Heer, Onno Bende
1Sanquin Research, Plesmanlaan 125, 1066 CX, Amsterdam, The Netherlands. T.Rispens@sanquin.nl
Journal of the American Chemical Society
|June 2, 2011
概括
人类IgG4抗体经历Fab-arm交换,产生双特异性抗体. 这项研究揭示了慢慢的CH3域解离是关键障碍,Fab臂稳定了过程并影响了体内反应速率.
科学领域:
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- 免疫球蛋白G (IgG) 抗体通常是对称的二元体.
- 人类IgG4表现出独特的半分子交换 (Fab-arm交换),产生具有治疗潜力的双特异抗体.
- 控制IgG4 Fab臂交换的精确机制在很大程度上是未知的.
研究的目的:
- 为了阐明IgG4 Fab手臂交换的基本步骤和动力学.
- 为了确定分子间抗体重新排列的速度限制因素.
- 研究Fab域和氧化还原条件对交换过程的影响.
主要方法:
- 开发一个定量实时的Förster共振能量转移 (FRET) 测定.
- 监测抗体半分子交换的动力学.
- 对完整的IgG4和Fc片段进行比较分析.
主要成果:
- 非共价连接的CH3域的缓慢解离作用为内在的动力障碍.
- 模仿体内环境的还氧化条件显著降低了整体汇率.
- 与单独的Fc片段相比,Fab域稳定了共价异构体,增加了非共价异构体度和交换率.
结论:
- 这项研究阐明了IgG4 Fab-arm交换的机制,突出了CH3域相互作用和氧化还原控制.
- 法布-手臂交换动力学受到域间相互作用和局部细胞氧化还原环境的影响.
- 开发的FRET试验为抗体中的域间相互作用提供了准确的动力学数据.
相关概念视频
Antibody Structure
Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Antibody Structure
Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Transcytosis of IgG
Transcytosis is the process in which molecules are internalized by endocytosis, transported across the cell, and released through exocytosis from the opposite end of the cell. Molecules such as insulin, immunoglobulins, and certain nutrients are transferred through the recycling endosomes by recycling and transcytosis.
IgG molecules from a mother undergo transcytosis starting around 13 weeks of gestation. The amount of IgG transferred and entering the fetal blood circulation increases with...
IgG molecules from a mother undergo transcytosis starting around 13 weeks of gestation. The amount of IgG transferred and entering the fetal blood circulation increases with...
Antibody Structure and Classes
Antibodies, also known as immunoglobulins, are produced by B cells in response to foreign substances, such as bacteria and viruses. These proteins are critical for recognizing and neutralizing these substances, protecting the body from potential harm.
The basic structure of an antibody consists of four protein chains: two identical heavy chains and two identical light chains. These chains are held together by disulfide bonds and other non-covalent interactions, forming a Y-shaped structure.
The basic structure of an antibody consists of four protein chains: two identical heavy chains and two identical light chains. These chains are held together by disulfide bonds and other non-covalent interactions, forming a Y-shaped structure.
Antibody Actions
Antibodies, or immunoglobulins, are critical players in the immune system's arsenal against invading pathogens. Produced by B cells and plasma cells, their primary role is to detect and bind to specific antigens, molecules found on the surface of pathogens like bacteria or viruses. Beyond antigen recognition, antibodies perform several vital functions that contribute to immune defense.
Neutralization
Antibodies can bind to pathogens, preventing them from infecting host cells. This process...
Neutralization
Antibodies can bind to pathogens, preventing them from infecting host cells. This process...
B Cell Activation and Differentiation
The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...

