The human IgG anti-carbohydrate repertoire exhibits a universal architecture and contains specificity for microbial attachment sites

Schneider, Christoph; Smith, David F.; Cummings, Richard D.; Boligan, Kayluz Frias; Hamilton, Robert G.; Bochner, Bruce S.; Miescher, Sylvia; Simon, Hans‐Uwe; Pashov, Anastas; Vassilev, Tchavdar; Gunten, Stephan von

doi:10.1126/scitranslmed.3010524

Cited by 87 publications

(129 citation statements)

References 62 publications

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“…Normal human serum and intravenous immunoglobulin (IVIG) derived from it have previously been shown to contain antibodies that recognize many self-like determinants, including LNnT and LNT 22,24,25 . Interestingly, and by contrast, we did not detect such antibodies to LNnT in naïve rabbit serum, although it did contain antibodies to several of the CFG glycan determinants, and recognition against them was boosted after our immunization.…”

Section: Discussionmentioning

confidence: 99%

Intact Reducing Glycan Promotes the Specific Immune Response to Lacto-N-neotetraose-BSA Neoglycoconjugates

et al. 2015

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The mammalian immune system responds to eukaryotic glycan antigens during infections, cancer, and autoimmune disorders, but the immunological bases for such responses are unclear. Conjugate vaccines containing bacterial polysaccharides linked to carrier proteins (neoglycoconjugates) have proven successful, but these often contain repeating epitopes and the reducing end of the glycan is less important, unlike typical glycan determinants in eukaryotes, which are shorter in length and may include the reducing end. Here we have compared the effects of two linkage methods, one that opens the ring at the reducing end of the glycan, and one that leaves the reducing end closed, on the glycan specificity of the vaccine response in rabbits and mice. We immunized rabbits and mice with bovine serum albumin (BSA) conjugates of synthetic open- and closed-ring forms (OR versus CR) of a simple tetrasaccharide lacto-N-neo-tetraose (LNnT, Galβ1-4GlcNAcβ1-3Galβ1-4Glc), and tested reactivity to the immunogens and several related glycans in both OR and CR versions on glycan microarrays. We found that in rabbits the immune response to the CR conjugate was directed toward the glycan, whereas the OR conjugate elicited antibodies to the reducing end of the glycan and linker region but not specifically to the glycan itself. Unexpectedly, mice did not generate a glycan-specific response to the CR conjugate. Our findings indicate that the reducing end of the sugar is crucial for generation of a glycan-specific response to some eukaryotic vaccine epitopes, and that there are species-specific differences in the ability to make a glycan-specific response to some glycoconjugates. These findings warrant further investigation with regard to rational design of glycoconjugate vaccines.

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Section: Discussionmentioning

confidence: 99%

Intact Reducing Glycan Promotes the Specific Immune Response to Lacto-N-neotetraose-BSA Neoglycoconjugates

et al. 2015

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“…Such autoreactive specificities likely rely on poorly understood mechanisms for their maintenance in the glycan‐reactive B cell pool. Interestingly, certain glycan specificities are highly conserved in the human population, seemingly representing a set of core clonal specificities for certain glycan epitopes with small pockets of variability . Furthermore, it is clear that in many cases, NAb B cell clonotypes are conserved in the human population, possibly due to restricted antibody heavy chain variable region (IGHV) gene usage .…”

Section: The Development and Functions Of Natural Antibodiesmentioning

confidence: 99%

Manipulation of the glycan‐specific natural antibody repertoire for immunotherapy

New

King

Kearney

2016

Immunological Reviews

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Summary Natural immunoglobulin derived from innate-like B lymphocytes plays important roles in the suppression of inflammatory responses and represents a promising therapeutic target in a growing number of allergic and autoimmune diseases. These antibodies are commonly autoreactive and incorporate evolutionarily conserved specificities, including certain glycan-specific antibodies. Despite this conservation, exposure to bacterial polysaccharides during innate-like B lymphocyte development, through either natural exposure or immunization, induces significant changes in clonal representation within the glycan-reactive B cell pool. Glycan-reactive natural antibodies have been reported to play protective and pathogenic roles in autoimmune and inflammatory diseases. An understanding of the composition and functions of a healthy glycan-reactive natural antibody repertoire is therefore paramount. A more thorough understanding of natural antibody repertoire development holds promise for the design of both biological diagnostics and therapies. In this article we review the development and functions of natural antibodies and examine three glycan specificities, represented in the innate-like B cell pool, to illustrate the complex roles environmental antigens play in natural antibody repertoire development. We also discuss the implications of increased clonal plasticity of the innate-like B cell repertoire during neonatal and perinatal periods, and the prospect of targeting B cell development with interventional therapies and correct defects in this important arm of the adaptive immune system.

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“…Furthermore, polysaccharides, widely concerned as bioactive macromolecules in recent centuries, have been proved to benefit the intestinal health. Dietary polysaccharides can regulate the intestinal microenvironment and stimulate the macrophages or lymphocytes in gut tissues to fight against diseases like cancer (52). A recent study by Shade et al .…”

Section: Introductionmentioning

confidence: 99%

Cockroach allergen exposure and risk of asthma

Danh

Zhao

Gao

2016

Allergy

121

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Cockroach sensitization is an important risk factor for the development of asthma. However, its underlying immune mechanisms and the genetic etiology for differences in allergic responses remain unclear. Cockroach allergens identification and their expression as biologically active recombinant proteins has provided a basis for studying the mechanisms regarding cockroach allergens induced allergic sensitization and asthma. Glycans in allergens may play a crucial role in the immunogenicity of allergic diseases. Protease-activated receptor (PAR)-2, Toll-like receptor (TLR), and C-type lectin receptors have been suggested to be important for the penetration of cockroach allergens through epithelial cells to mediate allergen uptake, dendritic cell maturation, antigen presenting cell (APC) function in T cell polarization, and cytokine production. Environmental pollutants, which often co-exist with the allergen, could synergistically elicit allergic inflammation, and aryl hydrocarbon receptor (AhR) activation and signaling may serve as a link between these two elements. Genetic factors may also play an important role in conferring the susceptibility to cockroach sensitization. Several genes have been associated with cockroach sensitization and asthma-related phenotypes. In this review, we will discuss the epidemiological evidence for cockroach allergen-induced asthma, cockroach allergens, the mechanisms regarding cockroach allergens induced innate immune responses, and the genetic basis for cockroach sensitization.

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The human IgG anti-carbohydrate repertoire exhibits a universal architecture and contains specificity for microbial attachment sites

Cited by 87 publications

References 62 publications

Intact Reducing Glycan Promotes the Specific Immune Response to Lacto-N-neotetraose-BSA Neoglycoconjugates

Intact Reducing Glycan Promotes the Specific Immune Response to Lacto-N-neotetraose-BSA Neoglycoconjugates

Manipulation of the glycan‐specific natural antibody repertoire for immunotherapy

Cockroach allergen exposure and risk of asthma

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