In recent years, there has been growing interest in engineering Fc proteins and modifying the glycosylation of antibodies to enhance their therapeutic potential. Fc proteins are composed of two heavy chains and two light chains, each containing a variable (V) and a constant (C) region. The Fc region of antibodies is located at the C-terminal end of the heavy chain and is responsible for mediating effector functions. Fc proteins from different species can differ in their amino acid sequence and glycosylation patterns, leading to variations in their FcR binding and functional activity.
Fc Protein And Glycoengineered Antibodies involves modifying the amino acid sequence of the Fc region to enhance or reduce its effector functions. For example, the substitution of an asparagine residue at position 297 (N297) of the Fc region with other amino acids can abolish or enhance the binding of Fc to FcRs or complement. N297 is the site of N-linked glycosylation, which plays a critical role in modulating Fc function. The addition of a glycan at N297 can increase the binding of Fc to FcγRIIIa and enhance ADCC.
IgG is the most abundant antibody in the human body and is involved in fighting bacterial and viral infections. The Fc portion of IgG antibodies can bind to a variety of receptors on other cells, including Fcγ receptors on immune cells and FcRn receptors on endothelial cells. When IgG binds to an antigen, it triggers a series of immune responses that help to eliminate the pathogen.
Fcγ receptors are found on a variety of immune cells, including macrophages, neutrophils, and natural killer cells. When IgG binds to Fcγ receptors, it activates these cells and triggers the release of inflammatory mediators such as cytokines and chemokines. This leads to an influx of immune cells to the site of infection, where they can eliminate the pathogen.
FcRn receptors are found on the surface of endothelial cells in the blood vessels. When IgG binds to FcRn, it is protected from degradation and has a longer half-life in the bloodstream. This is important for maintaining a high concentration of antibodies in the blood and ensuring a rapid immune response to any pathogens that enter the body.
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