Carbohydrates and T cells: A sweet twosome

Avci, Fikri Y.; Li, Xiangming; Tsuji, Moriya; Kasper, Dennis L.

doi:10.1016/j.smim.2013.05.005

Cited by 88 publications

(60 citation statements)

References 72 publications

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“…This in turn stimulates carbohydrate specific T-cells (Tcarbs) and leads to the production of high-affinity carbohydrate specific IgGs. 39 , 41 , 42 Considering the mechanism of action in producing conjugate vaccines will help produce knowledge-based vaccines that are target specific, structurally better-defined, both immunogenic and protective, and produced at a much lower cost. 40 This will allow for use on a more global scale to help control pneumococcal infections.…”

Section: Discussionmentioning

confidence: 99%

Current status and future directions of invasive pneumococcal diseases and prophylactic approaches to control them

Wantuch

Avci

2018

Human Vaccines & Immunotherapeutics

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Streptococcus pneumoniae is a major human bacterial pathogen responsible for millions of deaths each year and significantly more illnesses worldwide. With over 90 different serotypes, providing effective vaccine programs has been a continuing challenge. Since 1983, the world has been introduced to four different pneumococcal vaccines (PPSV23, PCV7, PCV10, and PCV13) each with their own complications and successes. Since vaccination programs began, a decrease in the overall rate of pneumococcal pneumonia and associated diseases has been observed, notably in higher risk populations. However, with a decrease in incidence of vaccine type pneumococcal serotypes, increases in non-vaccine serotypes of the bacteria have been observed along with serotype switching. Additionally, a rise in antibiotic resistant strains of S. pneumoniae is noted. Here we discuss both the positive and negative clinical manifestations of pneumonia vaccine programs and discuss the challenges in pneumococcal vaccine design.

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Section: Discussionmentioning

confidence: 99%

Current status and future directions of invasive pneumococcal diseases and prophylactic approaches to control them

Wantuch

Avci

2018

Human Vaccines & Immunotherapeutics

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“…If the glycan is small enough, just one or two sugars as is the case for CSP and TRAP, these glycopeptides can be displayed by the MHC II for recognition by the T-cell receptor. Contrary to classical dogma, Kasper and coworkers have shown that glycopeptides are indeed true T-cell epitopes that can drive CD4 + T-cell help to B cells for the production of antibodies to the glycosylated antigen [4]. Furthermore, antibodies raised against a glycosylated vaccine should be better able to recognize native sporozoites, particularly if the glycosylated antigen represents an important T-cell epitope.…”

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confidence: 98%

“…This is probably because the exact nature of protein glycosylation in Plasmodium spp. has been contentious [2,3] and because glycopeptides were for a long time incorrectly thought to be T-independent antigens [4].Uncertainty surrounding protein glycosylation in Plasmodium parasites was driven in the past by an inability of common glycan-recognizing lectins to bind to parasite proteins and poor histological staining of parasites by periodic acid-Schiff methods. Indeed, it appeared that the installation of glycosylphosphatidylinositol anchors was the only type of glycosylation that Plasmodium parasites undertook [5].…”

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confidence: 99%

“…RTS,S/AS01 also induces CD8 + T-cell responses in some individuals. Since CSP is presented by MHC I on the surface of infected hepatocytes, and glycopeptides can indeed be presented by MHC I [4], it is possible that glycosylation could also contribute to CD8 + -dependent killing of liver stage parasites.…”

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Implications of Plasmodium Glycosylation on Vaccine Efficacy and Design

Goddard‐Borger

Boddey

2018

Future Microbiol.

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Malaria remains a dire public health problem, despite significant efforts to control and eliminate the disease, and is caused by infection with any one of six species of Plasmodium parasite. Although focused control measures have halved the number of annual deaths from malaria to approximately 630,000 [1], the disease is still endemic in 91 countries and resistance to antimalarials continues to spread. Malaria eradication will require a combination of control measures including a vaccine that affords effective protection against different species and strains of Plasmodium parasites; a need that is currently unmet. Although much has been written about the design and evaluation of malaria vaccines, relatively little has been said about the impact that glycosylation has on the efficacy of existing or emerging vaccine technologies. This is probably because the exact nature of protein glycosylation in Plasmodium spp. has been contentious [2,3] and because glycopeptides were for a long time incorrectly thought to be T-independent antigens [4].Uncertainty surrounding protein glycosylation in Plasmodium parasites was driven in the past by an inability of common glycan-recognizing lectins to bind to parasite proteins and poor histological staining of parasites by periodic acid-Schiff methods. Indeed, it appeared that the installation of glycosylphosphatidylinositol anchors was the only type of glycosylation that Plasmodium parasites undertook [5]. Genome sequencing of Plasmodium spp. also revealed the absence of genes required to build and remodel common eukaryotic glycans [2,3]. Even so, homologs of several genes required for protein glycosylation are present and conserved in the genomes of Plasmodium spp. and metabolomic analyses of parasite material has demonstrated the presence of the nucleotide sugars required for protein glycosylation, which alluded to the existence of as yet undiscovered parasite glycans.With the aid of modern protein mass spectrometry methods, several research groups have recently tackled the issues of glycan lability and relatively small sample sizes to begin characterizing the true diversity of Plasmodium protein glycosylation [6][7][8][9][10][11][12]. Evidence for the synthesis of short N-linked glycans has been reported in asexual blood stages of Plasmodium falciparum [6], and there is every reason to expect that these modifications will be found in other life cycle stages as well. Cell surface proteomic studies of P. falciparum and P. vivax sporozoites, the two species responsible for the majority of malaria cases and deaths, have demonstrated that O-and C-linked glycans exist on the essential adhesive proteins, TRAP and CSP [8,10]. These abundant surface proteins are required for parasite infectivity and are prime vaccine candidates because sporozoites represent a population bottleneck in the life cycle as parasites pass from mosquito to human and establish an infection in the liver. Moreover, strain-transcending sterile immunity can be achieved through strong B-and T-cell-dependent respons...

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Antigens: CarbohydratesII

Kieber-Emmons

Monzavi‐Karbassi

Kieber‐Emmons

2020

Encyclopedia of Life Sciences

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Glycosylation is critical for a wide range of biological processes across both normal and disease states. Carbohydrate antigens, for example, are polymeric chains of diverse monomeric sugar molecules that play a fundamental role in the pathogenicity and virulence of many organisms. Moreover, these pathogen‐associated glycan structures can also be found in association with other types of cells, including tumours. These types of glycan commonalities have helped generate critical discoveries in terms of glycan structure, allowing for the development of working hypotheses for their functions, in addition to the development of agents that target or mediate their expression levels. Therefore, through discussion of glycans as antigens, new insights of key molecular and cellular interactions between them and immune cells can be discerned, and the implication of these interactions in health and disease is enhanced. Numerous reviews and even this ELS series have described the structure of carbohydrates and glycans in general. Key Concepts Glycosylation is the most abundant post‐translational modification of proteins. Glycans expand the chemical diversity of the genetic code. Antigens are a collection of epitopes that affects recognition by the immune system. Antigens and immunogens are very different. Molecular mimicry of glycans profoundly affects the pathophysiology of infection and neoplasia. Lectin‐family receptors and antibodies have been used to define carbohydrate antigens. Clustering of epitopes defines glycan antigens better than nonclustered epitopes. Carbohydrate antigens can define danger signals to the immune system through pattern recognition receptors. Clustering associates with different B‐cell populations for processing as immunogens. MHC and T‐cell receptors see atoms in particular arrays, not as a single molecular species – hence cross‐reactivity with zwitterionic carbohydrate structures. While carbohydrate‐based vaccines have been developed, as cancer vaccines they are not as effective. Metabolism is the next frontier to understanding glycan expression patterns.

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Carbohydrates and T cells: A sweet twosome

Cited by 88 publications

References 72 publications

Current status and future directions of invasive pneumococcal diseases and prophylactic approaches to control them

Current status and future directions of invasive pneumococcal diseases and prophylactic approaches to control them

Implications of Plasmodium Glycosylation on Vaccine Efficacy and Design

Antigens: CarbohydratesII

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