Glycosylation of monoclonal and polyclonal human IgG influences of protein structure and physiological environments by Muhammad Farooq

Cover of: Glycosylation of monoclonal and polyclonal human IgG | Muhammad Farooq

Published by University of Birmingham in Birmingham .

Written in English

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Thesis (Ph.D) - University of Birmingham, Department of Immunology, Faculty of Medicine and Dentistry, 1998.

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Statementby Muhammad Farooq.
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Open LibraryOL17873209M

Download Glycosylation of monoclonal and polyclonal human IgG

A multitude of monoclonal IgG antibodies directed against a variety of therapeutic targets is currently being developed and produced by biotechnological companies. The biological activity of IgGs is modulated by the N‐glycans Cited by:   N-linked oligosaccharides were released from human and bovine polyclonal immunoglobulin G (IgG) obtained from commercial sources and also from a monoclonal IgG 1 secreted by murine B-lymphocyte hybridoma cells Cited by: IgG‐Fab Glycosylation.

It has been demonstrated that 15−20% of polyclonal human IgG molecules bear N‐linked oligosaccharides within the IgG‐Fab region, in addition to the conserved glycosylation site at Asn in the IgG Cited by: CAMPATH-1H is a recombinant humanized murine monoclonal immunoglobulin (IgG 1) which recognizes the CDw52 antigen of human lymphocytes, and has been the subject of clinical trials for the treatment of non-Hodgkin's lymphoma and rheumatoid e mapping by liquid chromatography–mass spectrometry was used to confirm the predicted amino acid sequences and profile glycosylation Cited by: Glycosylation of the IgG molecule has a profound impact on its biological functions.

Human IgG has only one conserved glycosylation site, each heavy chain bearing an N-glycan linked to asparagine in the CH 2 domain of Fc part. The Fc-linked glycans are biantennary N-glycans with different extents of core fucosylation, bisecting N-acetylglucosamine (GlcNAc Cited by:   It has previously been shown that in multiple myeloma (MM) each IgG paraprotein exhibits a unique oligosaccharide profile.

It has been assumed that this results from a clone specific glycosylation machinery. However, the abnormal physiological environment of the bone marrow in this disease may also affect normal plasma cells producing polyclonal by: IgG glycoforms with desirable functionality as next-generation therapeutic antibodies.

Thus, the Fc glycans are fertile ground for the improvement of the safety, functionality, and efficacy of therapeutic IgG antibodies in the era of precision medicine. KEYWORDS chemoenzymatic glycoengineering, crystal structure, endoglycosidase, fucose, glycosylation,Cited by: 1.

N-Linked Glycoforms from Human IgG or Industrial Glycosylation of monoclonal and polyclonal human IgG book. (A) A scheme of the human IgG N-glycosylation site asparagine (Asn) with a representative attachment of an oligosaccharide File Size: 1MB. In human IgG a second F ab glycosylation can occur on the kappa (V κ), lambda (V λ) or heavy chain (VH) with no consensus sequence (Jef feris b).

IgA1 contains two complex glycans (Asn scientifically justified. Monoclonal antibody (mAb) products are extraordinarily heterogeneous due to the presence of a variety of enzymatic and chemical modifications, such as deamidation, isomerization, oxidation, glycosylation File Size: 2MB.

Approximately 30% of polyclonal human IgG molecules bear N-linked oligosaccharides in the IgG Fab region, in addition to those attached at the conserved glycosylation site at Asn in the IgG Cited by: Abstract: Monoclonal antibodies (MAbs) are the fastest growing class of human pharmaceuticals.

More than 20 MAbs have been approved and several hundreds are in clinical trials in various therapeutic. Unlabelled polyclonal human IgG and glycosylated monoclonal IgG1 and anti-D (Rh) antibody inhibited the binding of I-labelled monomeric human IgG binding by U Fc gamma RI at concentrations.

Immunoglobulin G (IgG) is one of the most abundant proteins present in human serum and a fundamental component of the immune system. IgG3 represents ∼8% of the total amount of IgG in human serum and stands out from the other IgG subclasses Cited by: Unlabelled polyclonal human IgG and glycosylated monoclonal IgG1 and anti-D (Rh) antibody inhibited the binding of I-labelled monomeric human IgG binding by U Fc gamma RI at concentrations greater than fold lower than the aglycosylated monoclonal Cited by: IgG glycosylation accounts for 2 to 3% of total IgG molecular weight, which is relatively low compared with the 12 to 14% for IgM, IgD, and IgE.

IgG Fc has a conserved N-linked glycosylation site at Asn across all subclasses. On the other hand, sequence analysis shows that only about 20% of human IgG. Human IgG has only one conserved glycosylation site located in the Cγ2 domain [asparagine (Asn)].

The sugar core anchored to this glycosylation site plays a critical role in Cited by: The RAG F(ab) 2 ′ fragments cross-reacted with murine and human IgG, allowing to cross-link the mouse surface IgG expressed by IIAhuFcγRIIB1 cells and the human monoclonal IgG antibody bound Cited by: As elevated levels of glycated IgG have been detected in the plasma of patients with diabetes mellitus, a disease associated with increased susceptibility to infection, we have investigated whether glycation of MoAbs Cited by: Monoclonal antibody (mAb)-based blockade of programmed cell death 1 (PD-1) or its ligand to enable antitumor T-cell immunity has been successful in treating multiple tumors.

However, the structural basis of the binding mechanisms of the mAbs and PD-1 and the effects of glycosylation Cited by: 2. All four subclasses of human serum IgG contain a single N‐glycosylation site in the constant region of their heavy chain, which is occupied by biantennary, largely core‐fucosylated and partially truncated oligosaccharides, that may carry a bisecting N‐acetylglucosamine and sialic acid glycosylation Cited by: identify reparative human monoclonal antibodies distinct from conventional antibodies.

In this chapter, we discuss the therapeutic relevance of both polyclonal and monoclonal antibodies in clinic. For example, lack of core-fucoses on these N-glycans may lead to a drastic enhancement of antibody-mediated cellular cytotoxicity. Moreover, sialylation of Fc N-glycans determines the immunosuppressive properties of polyclonal IgG from human blood, which stimulates research into Fc glycosylation of human plasma IgG Cited by: Antibody glycosylation can be influenced by the cell in which it is produced, the conformation of the antibody and cell culture conditions.

the oligosaccharide profile of the polyclonal IgG Author: Roy Jefferis. Monoclonal therapeutics have exploited antibody glycosylation as a mechanism to potentiate the Fc-effector activities of mAbs [32–34].

Therefore, mAb glycosylation was assessed to determine if glycan structures were more highly predictive of potent antibody effector Cited by: A) Polyclonal gammopathies. heteregeneous increase in immunoglobulins involving more than one cell line, maybe cause by any of variety of infiammatory, infectuous or neoplastic disorder.

The most common conditions in the differential diagnosis of polyclonal gammopathy are listed in Table 1. B) Monoclonal.

Recombinant monoclonal IgG antibodies are used to study structure–function relationships and also therapeutically for treatment of cancer and diseases of the immune system, and establishing their glycosylation pattern will therefore be of interest The field of glycosylation analysis of recombinant IgG Cited by:   Selection of a human anti-RhD monoclonal antibody for therapeutic use: impact of IgG glycosylation on activating and inhibitory Fc gamma R functions.

Clin Immunol (2–3)–9. Cited by: 8. Binding of the Fc domain of Immunoglobulin G (IgG) to Fcγ receptors on leukocytes can initiate a series of signaling events resulting in antibody-dependent cell-mediated cytotoxicity (ADCC) and other important immune responses. Fc domains lacking glycosylation Cited by: IgG (consisting of IgG1, IgG2a, IgG2b, IgG3, and IgG4) is the most abundant antibody in normal human serum; accounting for % of the total immunoglobulin pool.

IgG is involved in placenta transfer, with the mother’s IgG. screen using polyclonal human IgG has been established previously as a high-throughput method to screen for the solubility of human mAbs It was shown that highly soluble antibodies have chromato. Selection of a human anti-RhD monoclonal antibody for therapeutic use: impact of IgG glycosylation on activating and inhibitory FcγR functions.

Clin. Immunol.– ().Author: Belinda M. Kumpel, Radka Saldova, Carolien A. Koeleman, Jodie L. Abrahams, Agnes Hipgrave Edervee. N-glycan analysis of polyclonal IgG showed unique N-glycan peaks with statistically significant chromatogram variation across the 4 studied groups.

PCA identified specific patterns of glycosylation Cited by: 1. The introduction of monoclonal antibodies revolutionized immunology. The development of human monoclonal antibodies was inspired primarily by the enormous clinical benefits promised by these. Polyclonal Antibodies vs. Monoclonal Antibodies: Production.

Polyclonal antibodies (pAbs) are mixture of heterogeneous which are usually produced by different B cell clones in the body. They can recognize and bind to many different epitopes of a single antigen.

Polyclonal. This so-called polyclonal antibody response is also typical of the response to infection by the human immune system. Antiserum drawn from an animal will thus contain antibodies from. Hence, the constant ratio of IgG glycoforms in human serum is predetermined by glycosylation at the level of the individual antibody-producing cell.

The anti-D fraction of polyclonal anti-D immunoglobulin compared to the total human IgG Cited by: 6. Main Difference – Monoclonal vs Polyclonal Antibodies.

Antibodies are a type of globular proteins produced by the plasma B cells in response to a specific antigen can be a foreign. Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers.

PLoS Genet. 9, e (). ArticleCited by: Monoclonal antibodies (mAbs) represent the major fraction of approved bio-therapeutics for the treatment of cancer, autoimmune disorders and inflammatory diseases [].N-linked glycosylation of immunoglobulin G (IgG) antibodies is an important biomarker that defines the therapeutic efficacy of mAbs or immune state of the human.

For example, lack of core-fucoses on these N-glycans may lead to a drastic enhancement of antibody-mediated cellular cytotoxicity.

Moreover, sialylation of Fc N-glycans determines the immunosuppressive properties of polyclonal IgG from human blood, which stimulates research into Fc glycosylation of human plasma IgG Cited by:   A study of immunoglobulin G glycosylation in monoclonal and polyclonal species by electrospray and matrix-assisted laser desorption/ionization mass spectrometry.

N-linked oligosaccharides were released from human and bovine polyclonal immunoglobulin G (IgG) obtained from commercial sources and also from a monoclonal IgG Cited by:   Multiple human polyclonal and monoclonal (auto)antibodies were analyzed for levels of variable domain glycosylation.

For samples, lectin (SNA) affinity chromatography, total and specific IgG immunoassays, monoclonal antigen-specific antibodies, and analysis of glycosylation Cited by:

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