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Role of IgG3 in Infectious Diseases

2019; Elsevier BV; Volume: 40; Issue: 3 Linguagem: Inglês

10.1016/j.it.2019.01.005

1471-4981

Timon Damelang, Stephen J. Rogerson, Stephen J. Kent, Amy W. Chung,

Monoclonal and Polyclonal Antibodies Research

IgG3 has been associated with enhanced control or protection against a range of intracellular bacteria, parasites, and viruses. IgG3 Abs are potent mediators of effector functions, including enhanced ADCC, opsonophagocytosis, complement activation, and neutralization, compared with other IgG subclasses. Future Ab-based therapeutics and vaccines should consider utilizing IgG3, based on features of enhanced functional capacity. Investigating the impact of glycosylation patterns and allotypes on IgG3 function may expand our understanding of IgG3 responses and their therapeutic potential. IgG3 comprises only a minor fraction of IgG and has remained relatively understudied until recent years. Key physiochemical characteristics of IgG3 include an elongated hinge region, greater molecular flexibility, extensive polymorphisms, and additional glycosylation sites not present on other IgG subclasses. These characteristics make IgG3 a uniquely potent immunoglobulin, with the potential for triggering effector functions including complement activation, antibody (Ab)-mediated phagocytosis, or Ab-mediated cellular cytotoxicity (ADCC). Recent studies underscore the importance of IgG3 effector functions against a range of pathogens and have provided approaches to overcome IgG3-associated limitations, such as allotype-dependent short Ab half-life, and excessive proinflammatory activation. Understanding the molecular and functional properties of IgG3 may facilitate the development of improved Ab-based immunotherapies and vaccines against infectious diseases. IgG3 comprises only a minor fraction of IgG and has remained relatively understudied until recent years. Key physiochemical characteristics of IgG3 include an elongated hinge region, greater molecular flexibility, extensive polymorphisms, and additional glycosylation sites not present on other IgG subclasses. These characteristics make IgG3 a uniquely potent immunoglobulin, with the potential for triggering effector functions including complement activation, antibody (Ab)-mediated phagocytosis, or Ab-mediated cellular cytotoxicity (ADCC). Recent studies underscore the importance of IgG3 effector functions against a range of pathogens and have provided approaches to overcome IgG3-associated limitations, such as allotype-dependent short Ab half-life, and excessive proinflammatory activation. Understanding the molecular and functional properties of IgG3 may facilitate the development of improved Ab-based immunotherapies and vaccines against infectious diseases. killing of an Ab-coated target cell by a cytotoxic effector cell through a nonphagocytic process. a process by which Abs can inhibit Plasmodium growth in the presence of monocytes. Fcγ-receptor-mediated antiviral activity, occurring when Ab bound to virus-infected target cells engages FcγR-bearing effector cells, (e.g., NK cells, monocytes, or macrophages). process by which innate immune phagocytic effector cells (e.g., neutrophils, macrophages, or monocytes) ingest or engulf other cells, organisms, or particles. amino acid differences in the constant region of either the heavy or light chains of an Ab within a subclass of Abs. the overall sum of binding strength of multiple affinities, often used to describe the accumulated strength of two Ab Fab arms with its antigens. destruction of bacterial cells, often be mediated by Abs. recombinant protein that can simultaneously bind two different types of antigens. special type of Abs that can recognize and block many strains of a particular pathogen (e.g., virus) from entering healthy cells. protein produced by the liver in response to inflammation or infection. process by which proliferating B cells rearrange constant region genes in the immunoglobulin heavy chain locus, switching from one class of immunoglobulin to another. protein complex involved in the complement system (innate immune system). protein cascade within the innate immune system; it is responsible for a rapid and nonspecific clearance of pathogens by attracting phagocytic cells. C1q binds an Ab, triggering the complement cascade via the classical pathway of complement activation. expressed on the surface of enveloped viruses. Ab domain that binds to antigens; involved in neutralization. tail region of an Ab that determines its innate immune effector functions. surface protein receptors for IgGs (broadly expressed by cells of hematopoietic origin); they are defined as either activating (FcγRI, FcγRIIa/c, FcγRIII) or inhibitory (FcγRIIb); they elicit or inhibit immune functions, respectively. post-translational modification whereby carbohydrates are attached to proteins (e.g., Abs) via certain enzymes. measure of the mean survival time of a molecule to reduce in half, its initial value (e.g., concentration). flexible amino acid sequence in the central part of the heavy chains of Abs; can be linked by disulfide bonds. mechanism changing the B cell production of an immunoglobulin from one isotype to another. Ab produced by a single clone of cells. MHC class I like molecule that functions to protect IgG from catabolism, mediates transport of IgG across epithelial cells, and is involved in antigen presentation. process by which the pathogen is marked by an opsonin, for example, an Ab, for ingestion, and eliminated by phagocytes. occurrence of different genetic forms among the members of a population or colony, or in the lifecycle of an individual organism. can simultaneously bind to multiple types of antigens. process that diversifies BCRs to improve antigen recognition; a high frequency of point mutations are generated within variable regions of expressed Igs; Abs with higher-affinity variants are thus generated. expressed on sentinel cells such as macrophages and dendritic cells; recognize structurally conserved molecules derived from pathogens. transfer of plasma membrane fragments from target cells to effector cells. symptomatic malaria without signs of severity or evidence of vital organ dysfunction. mechanism of genetic recombination that occurs only during the early stages of T and B cell maturation, generating unique BCRs; leads to the generation of Ab diversity.