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Chlamydial Lipopolysaccharide
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
The availability of synthetic structures and artificial glycoconjugate antigens obtained after conjugation to proteins enabled us to determine the epitope specificities of monoclonal antibodies against the Kdo region, obtained after immunization with chlamydiae or Retype bacteria (Fig. 3). The immunogenic properties of the artificial glycoconjugates were also investigated in mice (71). Relevant monoclonal antibodies were selected on the basis of binding to [1] the immunizing antigen, [2] LPS attached to plastic surfaces, [3] LPS imbedded in natural (sheep erythrocytes) or artificial (liposomal) membranes, [4] isolated chlamydial elementary bodies, or [5] chlamydial inclusions of infected monolayers. The results indicated that these monoclonal antibodies were 100-fold higher in affinity than those obtained after immunization with chlamydial elementary bodies from either C. psittaci or C. trachomatis (Fig. 4). Thus, the immunogenic and antigenic properties of the synthetic compounds are not only similar but superior to their natural counterparts.
Carbohydrate Histochemistry
Published in Joan Gil, Models of Lung Disease, 2020
Bradley A. Schulte, Russell A. Harley, Samuel S. Spicer
Macromolecules consisting entirely or partially of carbohydrate are important constituents of all biological systems. In animal tissues, homopolysaccharides made up exclusively of a single monosaccharide such as glycogen serve as primary energy reserves. Heteropolysaccharides consisting of two or more different sugars such as the glycosaminoglycans (GAGs), which are most often found linked to protein to form proteoglycans, are important structural components of connective tissues and of basement membranes. Other glycoconjugates (GCs) composed of saccharide side chains of varying degrees of complexity linked glycosidically to protein (glycoprotein) or lipid (glycolipid) are important elements of cell membranes and macromolecular secretions.
The Development of Improved Therapeutics through a Glycan- “Designer” Approach
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
The larger glycans can be recognized by gamma-delta T cell type (CD3+). These T-cell types are important in activation of innate immune system and their cytotoxic effect showed to be promising anti-tumor therapies, wound healing, or antiparasitic therapy (Wu et al., 2014). The γδT cells do not require MHC complex and are able to display antigen on their surface thus stimulate B-cell responses, DC and macrophages independently. Knowing Tcarb receptor’s affinity and with availability of glycan structure databases one may utilize this information to design tailored immunogenic or immunosenescent peptides and screen large peptide libraries. If, however, one aims to generate more T-cell specific immune responses the interest should be directed towards bacterial zwitterionic carbohydrates as these showed to be capable of inducing CD4+ T cell responses and regulate inflammatory responses (Cobb et al., 2004). Several studies have shown that glycopeptides are the key modulators of CD4+ T cells and some of the N-glycans showed to be essential for MHC class II-restricted CD4+T cell recognition (Malaker et al., 2017). For example, N-linked glycans on the tyrosinase activate the CD4+ T cells and any point mutations introduced in the glycosites yield the protein immunosenescent (Housseau et al., 2001). Figure 20.2 represents intricate effect of glycoconjugates on cell-mediated immune responses.
Molecular engineering tools for the development of vaccines against infectious diseases: current status and future directions
Published in Expert Review of Vaccines, 2023
Wenhui Xue, Tingting Li, Ying Gu, Shaowei Li, Ningshao Xia
Glycoconjugate vaccines have demonstrated efficacy in reducing the incidence of severe bacterial infections. These vaccines are produced by covalently linking bacterial polysaccharides and carrier proteins using chemical conjugation techniques (Figure 2e) [114]. Currently, licensed examples of glycoconjugate vaccines are available for Haemophilus influenzae type b [115], Neisseria meningitis [116], and Streptococcus pneumoniae [117]. Despite their proven safety and effectiveness, the production of glycoconjugate vaccines involves multiple steps and requires rigorous quality control. Additionally, the chemical conjugation process can be unpredictable, which limits the widespread application of these vaccines. Further research is needed to optimize the production process of glycoconjugate vaccines and develop alternative conjugation methods that can enhance their applicability [118].
The barrier and beyond: Roles of intestinal mucus and mucin-type O-glycosylation in resistance and tolerance defense strategies guiding host-microbe symbiosis
Published in Gut Microbes, 2022
The glycan structures are often capped with fucose or Sia, and will frequently form important antigenic structures including the ABO blood group determinants, Sda/Cad antigen, and Lewis structures, which are found on other glycoconjugates in the body.23 The great diversity of glycan structures, comprised of at least >100 unique structures as revealed through advanced mass spectrometry-based approaches,26–28 have long implied important biologic functions that have been traditionally challenging to define due to the complexity of glycosylation. We and others have focused in vivo studies in mice to provide definitive data on the expression and function of mucin-type O-glycans in the intestinal tract. These studies have revealed central roles of mucin-type O-glycans in innate host defense strategies that protect from inflammatory interactions with our commensal microbiota and infection-induced damage from enteric pathogens.
Breast cancer glycan biomarkers: their link to tumour cell metabolism and their perspectives in clinical practice
Published in Expert Review of Proteomics, 2021
Tomas Bertok, Veronika Pinkova Gajdosova, Aniko Bertokova, Natalia Svecova, Peter Kasak, Jan Tkac
Carbohydrates are the most common type of biomolecules on Earth and are ubiquitous for the most common enzymatic post-translational modification of proteins called glycosylation [26]. Complex carbohydrates – glycans, are a part of many glycoconjugates, such as glycopeptides and glycoproteins, peptidoglycans, glycolipids, lipopolysaccharides, glycosaminoglycans and other glycosides (Figure 2). Most common glycosylation is N- and O-glycosylation, where glycan part is attached to Asn-X-Ser/Thr or Ser/Thr residues, respectively, but there are less abundant glycans such as C-glycans (C-C bond via tryptophan) and the quite unusual S-glycans (C-S bond via cysteine) [27]. Changes in glycan structure and composition caused by different expression of glycan-modifying enzymes, i.e. glycosyltransferases („writers“) and glycosidases („erasers“) [28], are associated with pathological processes – including cancer, promoting cell proliferation, angiogenesis, epithelial-to-mesenchymal transition, migration or extravasation [29,30]. Aberrant glycoforms are present during development and progression of cancer (metastases) and might lead to chemoresistant cell lines [26]. While aberrant glycoforms of some membrane-bound glycoconjugates may directly serve as receptors for some viral hemagglutinins (Influenza virus), membrane-associated mucins create a physical barrier and also a „decoy“ for the pathogens to protect epithelial cells [26].