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The Inducible Defense System: Antibody Molecules and Antigen-Antibody Reactions
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
The Fab and Fc fragments of the Ig molecule differ in their attributes. The Fab fragment binds to antigen because it contains the antibody′s binding site. Fab fragments can combine with antigen to form soluble complexes, but they cannot precipitate antigens, as there is only one binding site on each fragment (Figure 7.7). The Fc portion does not bind to antigen but can be crystallized.
Immunoglobulins
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
The antibody hinge region and areas near it, due to their loose folding and exposure to solvent, are susceptible to proteases. The sulfhydryl protease papain cleaves the IgG hinge region yielding three antibody fragments (Figure 4–7). Two of these fragments are identical, and each bears one combining site. Since they react with antigen, these fragments are called Fab (antigen-binding). An Fab fragment contains a complete L chain, and the VH and CH1 domains of the H chain. The other papain cleavage product spontaneously crystallizes in cold, neutral solution and is called Fc. This fragment contains the CH2 and CH3 domains of the IgG H chains.
Immunoglobulins: Structure and diversity
Published in Gabriel Virella, Medical Immunology, 2019
The incubation of purified IgG with papain, a proteolytic enzyme extracted from the latex of Carica papaya, results in the splitting of the molecule into two fragments that differ in charge, antigenicity, biochemical characteristics, and biological functions. One of the fragments contains the binding site of the antibody and for that reason was designated as Fab, while the second fragment was found to be crystallizable and for that reason named Fc.
Challenges in antibody structure prediction
Published in mAbs, 2023
Monica L. Fernández-Quintero, Janik Kokot, Franz Waibl, Anna-Lena M. Fischer, Patrick K. Quoika, Charlotte M. Deane, Klaus R. Liedl
Antibodies are crucial components of the adaptive immune response.15 Genetic recombination and somatic hypermutation events enable the adaptive immune system to produce a vast number of antibodies against a variety of pathogens.14 To understand and optimize antigen recognition and to enable rational design of antibodies, accurate structure models are essential.16 Despite these recent advances, accurate structure prediction of antibodies remains challenging and still needs to be extensively validated. In particular, the flexible loops involved in recognizing the antigen pose a major challenge.17,18 In comparison to other protein superfamilies, the fold of antibodies is generally highly conserved.19–21 In particular, the framework of the antigen-binding fragment (Fab) is structurally almost identical for all antibodies.22,23 However, the area hardest to predict accurately is the six hypervariable loops that can form, together with several framework residues, the antigen-binding site, engaging with the respective epitope. These loops are also known as the complementarity-determining region (CDR) and provide the sequence and structure diversity essential to recognize a wide range of antigens. Five of the six loops tend to adopt canonical cluster folds based on their length and sequence composition. However, the third CDR loop of the heavy chain, the CDR-H3 loop, is the most diverse in length, sequence and structure and therefore is the most challenging loop to predict accurately.
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].