The Lymphatic/Immune System and Its Disorders
Walter F. Stanaszek, Mary J. Stanaszek, Robert J. Holt, Steven Strauss in Understanding Medical Terms, 2020
Each Y-shaped antibody or immunoglobulin is made up of two light peptide chains and two heavy chains. The arms of the Y form the variableregion, which differs for each specific antibody; the variable region contains the combining site(antigen-binding site) specific for the antigens to which they attach and can be split chemically to yield the Fab fragment(antigen-binding fragment). There are five different kinds of heavy chains providing the classification of immunoglobulins: IgA (or gA), IgG, IgD, IgE, and IgM.
Biologic Drug Substance and Drug Product Manufacture
Anthony J. Hickey, Sandro R.P. da Rocha in Pharmaceutical Inhalation Aerosol Technology, 2019
Structurally, Ig is commonly represented in a typical Y-arm structure (Figure 8.1) consisting of two large/heavy and two small/light polypeptide chains joined by disulfide bridges. Antibody fragments consist of a (mostly) constant region (designated, Fc) and an antigen-binding region (designated, Fab). Antibodies that recognize multiple sites of an antigen are termed polyclonal, whereas antibodies that target only a specific site are monoclonal. Identical immune cells make monoclonal antibodies, whereas polyclonal antibodies are produced by a mass of immune cells that may produce antibodies against different regions of the antigen. In industrial applications, monoclonal antibodies are prepared using recombinant DNA technology in cultured cells. For human clinical applications, monoclonal antibodies are generally preferred. Polyclonal antibodies are utilized for diagnostic and lab use such as immunohistochemistry.
Antibody-based Radionuclide Imaging
Michael Ljungberg in Handbook of Nuclear Medicine and Molecular Imaging for Physicists, 2022
Antibodies are heavy (~150 kDa) and Y-shaped globular plasma proteins, predominantly referred to as immunoglobulins (Ig). They consist of two regions, the antigen-binding fragment (Fab region) and the fragment crystallizable (Fc) region (Figure 18.1). The variable region of the Fab part is responsible for binding to specific antigens, while the Fc region interacts with immune cells and proteins. The Fc region also determines the antibody isotype: IgG, IgA, IgM, IgE, or IgD, each of which differs in function and distribution in the human body. For imaging and therapy, IgG is the most commonly used antibody isotype. Within IgG there are four subclasses: IgG1, IgG2, IgG3, and IgG4, each of which has a distinct role in the immune response. While the subtypes share 90 per cent similarity, small structural differences can lead to substantial changes in their in vivo behaviour. For example, the serum half-life of IgG1, IgG2, and IgG4 is approximately 21 days, while for IgG3 this is only 7 days [20, 21].
Recent advances and persistent challenges in the design of freeze-drying process for monoclonal antibodies
Published in Pharmaceutical Development and Technology, 2022
Hassana Hsein, Julie Auffray, Thierry Noel, Pierre Tchoreloff
The advent of mAbs in therapeutic field is essentially due to their specific recognition of biological targets correlated with a good safety profile. The safety profile has been significantly improved by decreasing the immunogenicity after administration thanks to the evolution of mAbs types from murine to chimeric, then to humanized and finally to human antibodies (Chiu et al. 2019). Target recognition and specificity are linked to the tridimensional structure and to the amino-acids sequence of these glycoproteins macromolecules, particularly to the crystallizable fragment (Fc) and the two antigen-binding fragment (Fab) of immunoglobulin G (IgG, the major isotype of antibodies) (Figure 1). The Fab fragments are essentially implicated in the antigen recognition and in the therapeutic specificity through different mechanisms of action, either by their neutralizing function or by their antagonist function after binding to the epitope. The Fc fragment is implicated in activating the immune system either by interacting with Fc-receptors on (innate) immune cells or by the recognition of proteins of the complement system. Due to the fundamental link between the mAb molecular structure and the target recognition, it is crucial to conserve the tridimensional structural integrity all over the mAb life cycle from formulation, process, and storage to the administration to patient (Wang et al. 2007; Chiu et al. 2019).
Inventive step assessment of top selling monoclonal antibodies in Brazil
Published in Expert Opinion on Therapeutic Patents, 2021
Louise Azulay Palavecino, Carlos Rangel Rodrigues, Murilo Lamim Bello, Alexandre Guimarães Vasconcellos
Monoclonal antibodies (mAbs) usually present a ‘Y’ shape with two heavy chains (HC) and two light polypeptide chains (LC). Each HC has three constant domains and one variable domain, whereas each LC has one constant domain and another variable domain. The fragment antigen-binding site (Fab) is responsible for antigen recognition, comprises the whole LC and one constant domain and one variable domain of HC [1]. Fab has the hypervariable region known as Complementarity-Determining Region (CDR), comprised only by the variable domain. Moreover, the framework region correctly orientates the CDR binding to the respective target through sulfide bounds. The cristallizable fragment (Fc) comprises the other two HC constant regions and binds to different types of Fc receptors (FcR) in immune cells, such as natural killers, monocytes, dentritic cells, B cells, and macrophages, triggering effector functions, such as antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) [2].
A perspective toward mass spectrometry-based de novo sequencing of endogenous antibodies
Published in mAbs, 2022
Sebastiaan C. de Graaf, Max Hoek, Sem Tamara, Albert J. R. Heck
Humoral human antibodies are complex proteins produced by B cells.7,19 Most antibody molecules (e.g., IgGs) are made up of four protein chains: two identical light chains and two identical heavy chains, which are interconnected by disulfide bridges (Figure 1). The light- and heavy-chain form two heterodimers, which are connected via disulfide bridges in the hinge region to form the intact antibody. Functionally, the intact antibody can be divided into two antigen-binding domains (also known as Fab or fragment antigen-binding) and a constant domain (also known as Fc or fragment crystallizable)22 (Figure 1a). The Fc is the effector entity of the antibody and can bind to Fc receptors on immune cells7 and mediate immune effector responses such as phagocytosis, antibody-dependent cell-mediated cytotoxicity, respiratory burst, and cytokine release.23 In contrast to the fully conserved sequence and structure of the Fc, the Fab is responsible for the vast diversity in recognized antigens and is thus hypervariable.
Related Knowledge Centers
- Antibody
- Immunoglobulin Heavy Chain
- Immunoglobulin Light Chain
- Monomer
- Paratope
- Epitope
- Antigen
- Complementarity-Determining Region
- N-Terminus
- Fragment Crystallizable Region