Antibody Fc

Author : Margaret Ackerman,Falk Nimmerjahn
Publisher : Academic Press
Page : 358 pages
File Size : 52,8 Mb
Release : 2013-08-06
Category : Medical
ISBN : 9780123948182

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Antibody Fc: by Margaret Ackerman,Falk Nimmerjahn Pdf

Antibody Fc is the first single text to synthesize the literature on the mechanisms underlying the dramatic variability of antibodies to influence the immune response. The book demonstrates the importance of the Fc domain, including protective mechanisms, effector cell types, genetic data, and variability in Fc domain function. This volume is a critical single-source reference for researchers in vaccine discovery, immunologists, microbiologists, oncologists and protein engineers as well as graduate students in immunology and vaccinology. Antibodies represent the correlate of protection for numerous vaccines and are the most rapidly growing class of drugs, with applications ranging from cancer and infectious disease to autoimmunity. Researchers have long understood the variable domain of antibodies, which are responsible for antigen recognition, and can provide protection by blocking the function of their target antigen. However, recent developments in our understanding of the protection mediated by antibodies have highlighted the critical nature of the antibody constant, or Fc domain, in the biological activity of antibodies. The Fc domain allows antibodies to link the adaptive and innate immune systems, providing specificity to a wide range of innate effector cells. In addition, they provide a feedback loop to regulate the character of the immune response via interactions with B cells and antigen-presenting cells. Clarifies the different mechanisms of IgG activity at the level of the different model systems used, including human genetic, mouse, and in vitro Covers the role of antibodies in cancer, infectious disease, and autoimmunity and in the setting of monoclonal antibody therapy as well as naturally raised antibodies Color illustrations enhance explanations of the immune system

Author : Tianlei Ying,Rui Gong
Publisher : Frontiers Media SA
Page : 118 pages
File Size : 55,9 Mb
Release : 2018-12-21
Category : Electronic
ISBN : 9782889456789

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Antibody Fc Engineering: Towards Better Therapeutics by Tianlei Ying,Rui Gong Pdf

Author : Theo Rispens,Gestur Vidarsson
Publisher : Elsevier Inc. Chapters
Page : 358 pages
File Size : 48,8 Mb
Release : 2013-08-06
Category : Medical
ISBN : 9780128060308

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Antibody Fc by Theo Rispens,Gestur Vidarsson Pdf

Immunoglobulins are a group of closely related glycoproteins composed of 82 to 96% protein and 4 to 18% carbohydrate. In humans, there are five classes of immunoglobulins, which differ in heavy-chain structure. Immunoglobulin G (IgG) is the major class of immunoglobulins in blood and can be further subdivided in subclasses. The four subclasses of IgG were discovered in the 1960s following extensive studies using specific rabbit antisera against human IgG myeloma proteins.1 They are designated IgG1, IgG2, IgG3, and IgG4, in order of decreasing abundance. Several decades of research has revealed subtle but profound differences among the subclasses. Each subclass has a unique profile with respect to antigen binding, immune complex formation, complement activation, triggering of effector cells, and placental transport (Table 9.1). In addition, IgG antibody responses to different types of antigens or pathogens often lead to marked skewing toward one of the subclasses. On the other hand, selective subclass deficiencies are usually not detrimental to the individual but do sometimes lead to enhanced susceptibility toward specific classes of pathogens. All in all, the acquired variability within the Ig locus seems to have been selected for beneficial changes during evolution for optimizing or fine-tuning the antibody-mediated immune response.

Author : Guido Ferrari,Georgia Tomaras,R. Keith Reeves,Gabriella Scarlatti
Publisher : Frontiers Media SA
Page : 273 pages
File Size : 43,5 Mb
Release : 2020-07-28
Category : Electronic
ISBN : 9782889638901

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Fc-Mediated Antibody Functions and Fc-Receptor Polymorphism by Guido Ferrari,Georgia Tomaras,R. Keith Reeves,Gabriella Scarlatti Pdf

Author : Victor Raúl Gómez Román,Joseph C. Murray,Louis M. Weiner
Publisher : Elsevier Inc. Chapters
Page : 358 pages
File Size : 40,7 Mb
Release : 2013-08-06
Category : Medical
ISBN : 9780128060223

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Antibody Fc by Victor Raúl Gómez Román,Joseph C. Murray,Louis M. Weiner Pdf

Antibody-dependent cellular cytotoxicity (ADCC), also called antibody-dependent cell-mediated cytotoxicity, is an immune mechanism through which Fc receptor-bearing effector cells can recognize and kill antibody-coated target cells expressing tumor- or pathogen-derived antigens on their surface. Numerous associations between ADCC activity, Fc receptor polymorphisms, and clinical outcomes have been observed in both the settings of vaccination and monoclonal antibody therapy. Here, the effector cells and receptors involved in ADCC are introduced, followed by a description of the four main stages and mechanisms leading to the antibody-dependent effector-mediated killing of the target cell: (1) Recognition of the target cell and Fc receptor cross-linking on the surface of the effector cell; (2) phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) by cellular src kinases within the effector cell; (3) triggering of three main downstream signaling pathways in the effector cell, resulting in cytotoxic granule polarization and release; and (4) killing of the target cell via the predominant perforin/granzyme cell death pathway. Further, a summary and a discussion are presented in relation to case studies in which in vitro ADCC activity correlates with protection against infectious diseases and outcomes in monoclonal antibody therapy of cancer in vivo . The means by which these mechanisms are currently being exploited by recombinant antibody engineering, and a path toward a future in which designed vaccines take advantage of variant ADCC activity are also discussed. Throughout the chapter, attention is drawn to the fact that, while the majority of ADCC studies have been based on research using peripheral blood mononuclear cells in which NK cells have been assumed to be the main effectors, questions remain unanswered about ADCC mediated by non-NK cell populations in peripheral blood and in mucosal compartments.

Author : Roy Jefferis
Publisher : Elsevier Inc. Chapters
Page : 358 pages
File Size : 50,6 Mb
Release : 2013-08-06
Category : Medical
ISBN : 9780128060384

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Antibody Fc by Roy Jefferis Pdf

Diversity of antigen-binding specificity may be considered the hallmark of antibodies; however, the human IgG-Fc region also exhibits binding specificity for multiple ligands. Evolution of the IgG-Fc has resulted in the generation of interaction sites for endogenous (self) ligands that recruit and activate mechanisms facilitating the removal and destruction of antibody–pathogen immune complexes. However, pathogens (bacteria and virus) have co-evolved to elaborate IgG-Fc binding proteins that seek to subvert these protective mechanisms. The four human IgG subclasses exhibit differential binding specificity for these ligands, and the choice of IgG subclass for an antibody therapeutic allows selection for a ligand binding profile appropriate for the intended use. The profile of IgG-Fc ligand binding specificities is being extended through the generation and selection among multiple IgG-Fc mutant proteins. Of particular interest has been the development of mutant aglycosylated antibodies that retain or acquire ligand binding activities. This extends possible production vehicles to include prokaryotic systems, although an increased potential for inducing anti-drug antibodies may be a limiting factor.

Author : Peter Sun
Publisher : Elsevier Inc. Chapters
Page : 358 pages
File Size : 55,7 Mb
Release : 2013-08-06
Category : Medical
ISBN : 9780128060285

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Antibody Fc by Peter Sun Pdf

Molecular mechanisms of antibody-mediated Fc receptor activation have long been an interest in both Fc receptor biology and antibody therapeutics. The structural efforts to elucidate antibody recognition by Fc receptors have led to the generation of several crystal structures of antibody Fc fragments complexed with Fc receptors. Collectively, these structures revealed a conserved receptor binding mode for IgG and IgE, distinct from those for the neonatal Fc receptor (FcRn), protein A, and protein G. Fcγ receptor recognition in the lower hinge region allows enhanced antigen recognition through dimeric Fabs but obligates immune-complex formation for receptor activation. It also provides the basis for Fcγ receptors to differentiate among IgG subclasses. More recently, pentraxins have also been shown to bind and activate Fc receptors, and structural efforts to elucidate pentraxin Fcγ receptor recognition have revealed surprising similarities between pentraxins and immunoglobulins in Fc receptor recognition. This review summarizes the structural findings that formed the basis of modern antibody–Fc receptor biology and recent advances of shared Fc receptor recognition by innate pentraxins.

Author : Anonim
Publisher : Unknown
Page : 0 pages
File Size : 54,7 Mb
Release : 2018
Category : Electronic
ISBN : OCLC:1368429752

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Antibody Fc Engineering: Towards Better Therapeutics by Anonim Pdf

Monoclonal antibodies and Fc-fusion proteins used clinically are Fc-based therapeutics that grow fastest in the pharmaceutical industry. Since they both contain an Fc fragment, engineering of Fc fragments could be a platform for improving Fc-based drug efficacy. Fc engineering includes various aspects: stabilization of Fc; regulation of effector functions including antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity; extension of serum half-life by modification of neonatal Fc receptor (FcRn) binding; monomerization or heterodimerization of Fc for design of new Fc formats. Currently, many new methods are being used in Fc engineering. Compared to traditional methods such as site mutagenesis on certain positions by amino acid replacement, new methods such as display-based technology can confer high throughput screening and obtain optimized variants relatively quickly, accelerating the drug development process. With the new methods, many new Fc variants were identified. On this Research Topic we are going to review the progress in current Fc engineering including the new engineering methods and the Fc variants or constructs they have produced, and the potential of these new Fcs in clinical use.

Author : Jeffrey V. Ravetch,Falk Nimmerjahn
Publisher : Springer Nature
Page : 150 pages
File Size : 51,5 Mb
Release : 2019-09-03
Category : Medical
ISBN : 9783030310530

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Fc Mediated Activity of Antibodies by Jeffrey V. Ravetch,Falk Nimmerjahn Pdf

This volume explores several aspects of how antibodies mediate their activity in vivo, ranging from cancer immunotherapy to autoimmunity, infection, and vaccination. Divided into seven chapters, it provides in-depth insights into how antibodies and especially the antibody fragment crystallizable (Fc) domain modulate immune responses and antibody activity. The book begins by discussing evolutionary aspects of how the family of Fc receptors that are the key molecules for antibody activity evolved. In turn, it addresses the molecular and cellular pathways underlying IgG activity in cancer immunotherapy, and focuses on how IgG glycosylation regulates IgG and IgE activity in autoimmunity, allergy and infection. In closing, it presents strategies for developing novel antibody-based vaccination approaches. The book is intended for a very broad readership, including graduate students, postdocs and principal investigators with a basic grasp of immunology.

Author : Robert M. Anthony
Publisher : Elsevier Inc. Chapters
Page : 358 pages
File Size : 54,9 Mb
Release : 2013-08-06
Category : Medical
ISBN : 9780128060377

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Antibody Fc by Robert M. Anthony Pdf

IgG antibodies are highly potent molecules, with the unique ability to link foreign particles to innate immune cells. IgG antibodies recognize antigens with high affinity and bind cellular Fc receptors with low affinity individually. These interactions occur in the form of immune complexes, resulting in high-avidity interactions. In fact, the effector functions triggered by IgG antibodies are highly dependent on the type of Fc receptor that is bound; however, many aspects can influence Fc receptor binding by IgG antibodies, including the IgG isotype and the composition of the glycan on the IgG antibody. Further, FcγR expression is not stagnant but instead is affected by the inflammatory milieu. These considerations, and others that affect targeting of IgG Fcs to specific FcγRs to elicit desired effector functions, are discussed herein.

Author : Luisa Martinez-Pomares
Publisher : Elsevier Inc. Chapters
Page : 358 pages
File Size : 44,7 Mb
Release : 2013-08-06
Category : Medical
ISBN : 9780128060261

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Antibody Fc by Luisa Martinez-Pomares Pdf

This chapter offers an overview of the basic biology of phagocytes, macrophages, dendritic cells, and neutrophils and how it is affected by receptors for the Fc portion of antibodies (FcRs), particularly FcγRs. We focus on important processes such as phagocytosis and antigen presentation but it must be considered that these occur within the context of inflammation, where the complementary roles of the different phagocyte populations are clearly exposed. For this purpose, a brief description of the inflammatory response has also been included. Finally, research in innate immunity is coming to terms with the wide range of responses that can be achieved by selective engagement of pattern-recognition receptors, and we provide examples of how receptors not normally associated with responses to immunocomplexes modulate cellular activation mediated by FcRs.

Author : Brian Moldt,Ann J. Hessell
Publisher : Elsevier Inc. Chapters
Page : 358 pages
File Size : 47,8 Mb
Release : 2013-08-06
Category : Medical
ISBN : 9780128060292

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Antibody Fc by Brian Moldt,Ann J. Hessell Pdf

Author : Xiaojie Yu,Kavitha Baruah,Christopher N. Scanlan,Max Crispin
Publisher : Elsevier Inc. Chapters
Page : 358 pages
File Size : 49,6 Mb
Release : 2013-08-06
Category : Medical
ISBN : 9780128060315

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Antibody Fc by Xiaojie Yu,Kavitha Baruah,Christopher N. Scanlan,Max Crispin Pdf

The antibody Fc region is posttranslationally modified by N-linked glycosylation. In immunoglobulin G (IgG), the processing of the glycans is restricted by the presence of extensive interaction with the protein surface. The resulting set of antibody glycoforms exhibit a range of effector functions. In this chapter, we outline the impact of glycosylation on the immune function of antibodies and discuss the implications for monoclonal antibody and intravenous immunoglobulin therapies.

Author : Stefan S. Weber,Annette Oxenius
Publisher : Elsevier Inc. Chapters
Page : 358 pages
File Size : 41,6 Mb
Release : 2013-08-06
Category : Medical
ISBN : 9780128060230

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Antibody Fc by Stefan S. Weber,Annette Oxenius Pdf

In humans and mice there exist a multitude of Fcγ receptors (FcγRs) with different affinities and specificities for the different IgG subclasses. Engagement of FcRs on cells usually results in the initiation of an activating or inhibitory signaling cascade that can lead to multiple effector functions, including phagocytosis of opsonized pathogens or immune complexes. In this chapter, we discuss phagocytic cell types and their respective FcγRs that they utilize to phagocytize IgG-coated particles/pathogens. Furthermore, we discuss downstream signaling mechanisms and resulting effects of FcγR-mediated phagocytosis. Special emphasis is given to the role of FcR-mediated phagocytosis in phagocytes for pathogen uptake, subsequent intracellular localization, and pathogen control.

Author : Joseph U. Igietseme,Xiaoping Zhu,Carolyn M. Black
Publisher : Elsevier Inc. Chapters
Page : 358 pages
File Size : 52,8 Mb
Release : 2013-08-06
Category : Medical
ISBN : 9780128060360

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Antibody Fc by Joseph U. Igietseme,Xiaoping Zhu,Carolyn M. Black Pdf

Fc receptor (FcR)-dependent effector functions of antibodies contribute significantly to protective immunity against microbial pathogens and tumors. Therefore, FcR-mediated immunological processes constitute a key component of the immune system’s defense armamentaria for maintaining the biological and physiological integrity of the mammalian host who is yoked with frequent encounters with infections and neoplasia. The direct effector functions that result from FcR triggering are phagocytosis, antibody-dependent cellular cytotoxicity, and induction of inflammation; also, FcR-mediated processes provide immunoregulation and immunomodulation that augment T-cell immunity and fine-tune immune responses against antigens. This plasticity of effector and immunoregulatory functions provides unique opportunities to apply FcR-based platforms and immunotherapeutic regimens for vaccine delivery and drug targeting against infectious and non-infectious diseases. This chapter focuses on the protective immunological processes resulting from antibody or immune complex binding to FcRs on effector cells (i.e., NK cells, macrophages, dendritic cells, PMNs, and eosinophils), as well as innovative strategies to apply these mechanisms in immunotherapy, vaccine, and drug delivery against infectious and non-infectious diseases. Deleterious immune reactivity associated with FcR engagement, including immune complex diseases, allergic reactions due to IgE-mediated activation of mast cells and basophils, or facilitation of microbial infectivity, such as antibody-mediated enhancement of infections, are outside the focus of this review.