Related Experiment Video
Updated: Jul 13, 2025
06:29
Methods for Quantitative Detection of Antibody-induced Complement Activation on Red Blood Cells
Published on: January 29, 2014
30.6K
The Influence of Human IgG Subclass and Allotype on Complement Activation.
Timon Damelang1,2,3, Steven W de Taeye1,2, Rosa Rentenaar1
1Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Journal of Immunology (Baltimore, Md. : 1950)
|October 16, 2023
Summary
Structural variations in immunoglobulin G (IgG) allotypes significantly impact complement activation and complement-dependent cytotoxicity (CDC). Specific IgG2 variants and differences between IgG1 and IgG3 subclasses influence cell lysis, offering insights for therapeutic antibody design.
Area of Science:
- Immunology
- Molecular Biology
- Biochemistry
Background:
- Complement activation via the classical pathway is initiated by C1 binding to oligomeric immunoglobulins (Igs) on target surfaces.
- Antibody (Ab) structure, including isotype, subclass, and glycosylation, influences complement system activation.
- Polymorphic variants of IgG can affect Fc-dependent effector functions.
Purpose of the Study:
- To assess complement binding, deposition, and complement-dependent cytotoxicity (CDC) of 27 known IgG allotypes with anti-trinitrophenyl specificity.
- To investigate the impact of structural variations within IgG subclasses on complement activation.
- To elucidate the context-dependent nature of antibody-mediated CDC.
Main Methods:
- Evaluation of complement binding and deposition across 27 IgG allotypes.
- Assessment of complement-dependent cytotoxicity (CDC) using various cell lines (human RBCs, Ramos, Raji, Wien133).
- Comparison of IgG1 and IgG3 subclasses under varying antigen density and in the presence/absence of complement regulators.
Main Results:
- Minor differences in complement activation were observed among IgG1, IgG3, and IgG4 allotypes, with more substantial variations in IgG2.
- Allelic variant IGHG2*06 demonstrated reduced complement activation and CDC compared to other IgG2 polymorphisms.
- Cell lysis varied between IgG1 and IgG3, with IgG3 showing superior lysis of RBCs and Ramos cells, while IgG1 was more effective against Raji and Wien133 cells.
- Antigen density and antibody hinge length, rather than complement regulators, determined the context-dependent CDC activity of IgG1 and IgG3.
Conclusions:
- Single amino acid changes and hinge length differences in IgG allotypes can alter their capacity to activate complement.
- These variations may provide new insights into susceptibility to infectious, alloimmune, and autoimmune diseases.
- Understanding these structural-functional relationships can aid in the design of improved antibody-based therapeutics.
More Related Videos
Related Concept Videos
01:10Antibody Structure
60.2K
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...
60.2K
01:36Humoral Immune Responses
72.8K
Overview
72.8K
01:26Antibody Actions
1.1K
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...
1.1K
01:25Antibody Structure and Classes
931
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.
931
01:27Complement System
2.4K
The complement system is a group of approximately 20 plasma proteins that strengthen the body's defenses against infections through opsonization, inflammation, and cell lysis. Opsonization involves coating pathogens with complement proteins, making them more recognizable and facilitating phagocyte engulfment. Certain complement proteins induce inflammation that attracts immune cells to the site of infection. Cell lysis involves the destruction of pathogens through the formation of a...
2.4K
01:15Transcytosis of IgG
2.8K
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...
2.8K