• The 1B1 monoclonal antibody specifically binds to mouse CD1d, a 48-kDa glycoprotein with structural homology to major histocompatibility complex (MHC) class I molecules. (bdbiosciences.com)
  • Unlike conventional T cells, which mostly recognise peptide antigens presented by MHC molecules, i NKT cells recognise glycolipid antigens presented by the non-polymorphic MHC class I-like molecule, CD1d . (immunology.org)
  • NKT cells recognize lipid antigen presented in the context of CD1d molecules. (umaryland.edu)
  • NKT cells recognise and respond to glycolipid antigens presented on CD1d molecules. (sicollaborative.org)
  • molecules and recognize lipids Bcl-w and glycolipids as antigens. (pdgfrsignals.com)
  • These structures provide clues as to how CD1 molecules load glycolipids as well as data to guide the design of new therapeutic agents. (ox.ac.uk)
  • 2011 A unifying feature of αGC analogs that induce predominantly Th2 cell-associated cytokines is that they are more polar than KRN7000 and can load directly onto CD1d molecules on the cell surface (Im et?al. (biotech-angels.com)
  • 2012 However other studies yielded different conclusions identifying pharmacokinetic properties of the glycolipids or localization of CD1d molecules containing bound glycolipids to different membrane microdomains as major determinants of cytokine skewing in the response to iNKT cell activation (Im et?al. (biotech-angels.com)
  • Interaction of CD8α+ dendritic cells (DCs) with iNKT cells during presentation of Th1 cell-biasing versus Th2 cell-biasing glycolipid antigens led to markedly different changes in expression of costimulatory and coinhibitory molecules on these. (biotech-angels.com)
  • They are unique in their restriction to lipid antigens presented in CD1d molecules, which underlies their role in lipid-driven disorders such as obesity and atherosclerosis. (ox.ac.uk)
  • Unlike conventional T cells that recognize peptide antigen presented by major histocompatibility complex (MHC) molecules, NKT cells recognize glycolipid antigen presented by a molecule called CD1d. (wikidoc.org)
  • Invariant natural killer T (iNKT) cells are a subset of nonconventional T cells recognizing endogenous and/or exogenous glycolipid antigens in the context of CD1d molecules. (ox.ac.uk)
  • Alpha-galactosylceramide (α-GalCer) is a glycolipid that can be loaded into MHC-class-I-related CD1d molecules by dendritic cells and has been shown to stimulate invariant natural killer T (iNKT) cells. (tmu.edu.tw)
  • Kronenberg's work had a major impact in defining how glycolipid antigens are taken into cells and processed in lysosomes and unraveled the intracellular traffic of CD1d, which is the MHC class I molecule that presents lipid antigens. (wikipedia.org)
  • NKT cells are a subtype of T cells, found in low frequency in the body (less than 1% in the peripheral blood of mice and humans) and characterized by their reactivity to glycolipids presented in the context of an MHC class I-like molecule, called CD1d. (fapesp.br)
  • Graphical Abstract Introduction Natural killer T?cells with invariant T?cell receptor α chains (iNKT cells) are a conserved population that recognizes KM 11060 glycolipid antigens bound to CD1d a lipid antigen-presenting molecule with structural similarities to major histocompatibility complex (MHC) class I proteins (Brennan et?al. (biotech-angels.com)
  • Among them, the MHC class I-like molecule CD1d interacts with glycolipids and presents them to iNKT cells, mediating their activation. (cirn-na.com)
  • The iNKTCR recognizes lipid antigens on CD1d (an MHC class I like molecule, that is NOT polymorphic), so they can target multiple types of cancer (by recognizing tumor-derived glycolipids) using multiple mechanisms that are independent of protein tumor antigen and MHC restrictions. (molecule-world.com)
  • We also present the CD1d structure without lipid, which has a more open conformation of the binding groove, suggesting a dual conformation of CD1d in which the 'open' conformation is more able to load lipids. (ox.ac.uk)
  • We report that activation of human APCs by Toll-like receptor ligands (TLR-L) modulates the lipid biosynthetic pathway, resulting in enhanced recognition of CD1d-associated lipids by iNKT cells, as defined by IFN-gamma secretion. (ox.ac.uk)
  • In our hands the vast majority of these TCR β+ NK1.1+ cells are i NKT cells as evidenced by MRS1477 their reactivity with glycolipid-loaded CD1d tetramer (Fig. 5a). (crispr-reagents.com)
  • It appears to recognize CD1d only in association with β2m. (bdbiosciences.com)
  • iNKT specifically recognize the glycolipid alpha-galactosylceramide in the context of CD1d resulting in their activation. (eur.nl)
  • Invariant natural killer T cells recognize glycolipids from pathogenic Gram-positive bacteria. (bvsalud.org)
  • Finally, using soluble tetrameric iNKT T cell receptors (TCR) as a staining reagent, we demonstrate specific up-regulation of CD1d-bound ligand(s) on TLR-mediated APC maturation. (ox.ac.uk)
  • Scavenger receptors target glycolipids for natural killer T cell activation. (uchicago.edu)
  • i NKT cells are frequently characterised by the recognition of the prototypical glycolipid, a-galactosylceramide ( a-GalCer ), a marine-sponge-derived agent, which also potently activates them and has strong anti-tumour activity. (immunology.org)
  • 2012 Studies of the prototypical glycolipid antigen of iNKT cells an α-galactosylceramide (αGC) known as KRN7000 show the potential for iNKT cells to KM 11060 activate a range of immune effector functions in?vivo. (biotech-angels.com)
  • This is a feature consistently found for glycolipids that require cellular uptake for intracellular loading onto CD1d Im et al. (buildconenterprises.com)
  • 2011 In contrast glycolipids that induce responses that are biased toward Th1 cell cytokines are more hydrophobic and require intracellular loading onto CD1d for presentation (Arora et?al. (biotech-angels.com)
  • The crystal structure of human CD1d with and without alpha-galactosylceramide. (ox.ac.uk)
  • The glycolipid alpha-galactosylceramide binds with high affinity to CD1d and stimulates natural killer T cells. (ox.ac.uk)
  • Here we report the crystal structure of human CD1d in complex with synthetic alpha-galactosylceramide at a resolution of 3.0 A. The structure shows a tightly fit lipid in the CD1d binding groove, with the sphingosine chain bound in the C' pocket and the longer acyl chain anchored in the A' pocket. (ox.ac.uk)
  • In addition to TLR ligands, CD1d-restricted invariant NKT (iNKT) cells have been shown to efficiently promote the transactivation of DCs through the CD40L-CD40 interaction upon recognition of the CD1d-glycolipid antigen complex by their semi-invariant TCR. (biomedcentral.com)
  • The molecular basis for recognition of CD1d/a-galactosylceramide by a human non-Va24 T cell receptor. (uchicago.edu)
  • iNKT cells have been traditionally defined by the expression of an invariant TCR α-chain (Vα14-Jα18 in mice or Vα24-Jα18 in humans) and their capacity to recognise the glycolipid antigen α-galactosylceramide (αGalCer) presented on CD1d. (elifesciences.org)
  • Many hematopoietic cell types express CD1d and so are with the capacity of presenting glycolipid antigens to invariant natural killer T?cells (iNKT cells). (biotech-angels.com)
  • Alternatively, the adjuvant activity of CD1d-restricted invariant NKT cells (iNKT) on the innate and adaptive immunity is well demonstrated, and several CD1d glycolipid ligands are under pre-clinical and clinical evaluation. (biomedcentral.com)
  • α-Galactosylceramide (α-GC) is a synthetic glycolipid that is recognized by the invariant T-cell receptor of invariant natural killer T (iNKT) cells in a CD1d-restricted manner. (elsevierpure.com)
  • 2003 Several models have been put forth to explain how variations in the structure of glycolipid antigens lead to different outcomes of iNKT cell activation. (biotech-angels.com)
  • APC-derived soluble factors further increase CD1d-restricted iNKT cell activation. (ox.ac.uk)
  • However, CD1d expression was not detectable via flow cytometry on intestinal epithelial cells in studies using the anti-CD1d mAbs 3C11, 1B1, and 9C7. (bdbiosciences.com)
  • By visualizing glycolipid antigen presentation directly with monoclonal antibodies specific for complexes of αGC bound to CD1d we showed that the CD8α+DEC-205+ subset of dendritic cells was the major APC in the spleen for a range of αGC analogs irrespective of their chemical structures and cytokine biasing activities. (biotech-angels.com)
  • Simplexide induces CD1d-dependent cytokine and chemokine production from human monocytes. (cirn-na.com)
  • ii) CD1d knockdown inhibits monocyte activation by simplexide and iii) simplexide induces cytokine production from CD1d-transfected but not parental C1R cell line. (cirn-na.com)
  • Cultures containing i NKT cells that were sorted based on their binding to CD1d tetramer contained high background cytokine levels (data not shown) which is consistent with their partial activation by CD1d tetramer reagents leading to spontaneous cytokine secretion.38 Therefore we stained and isolated hepatic NKT cells based on their concomitant expression of TCR β and NK1.1 and according to standard protocols. (crispr-reagents.com)
  • The synthesis and processing of glycolipids and other potential endogenous lipid antigens depends on metabolic demand and may steer iNKT cells toward adopting a Th1 or Th2 signature. (ox.ac.uk)
  • Dr. Webb is a leading immunologist and research scientist who is recognized for her studies focused on the modulation of CD1d-mediated NKT cell activation for cancer immunotherapy using natural and artificial platforms. (umaryland.edu)
  • Furthermore, CD1d-dependent responses by NKT cells were required for activation and host protection . (bvsalud.org)
  • Thus, as myeloid antigen-presenting cells (APCs) such as monocytes, dendritic cells (DCs) and myeloid-derived suppressor cells (MDSCs) constitutively express CD1d, NKT cells are able to interact with these APCs not only during times of immune activation but also in immunologically quiescent periods. (pdgfrsignals.com)
  • In Specific Aim 1, we will perform a series of in vitro studies in primary murine and human cells to determine how the adjuvant combination affects CD1d Ag presentation and activation and functional differentiation of NKT cells into different effector subsets. (grantome.com)
  • Activation and tumor targeting of iNKT cells via recombinant α-galactosylceramide (αGC)-loaded CD1d-anti-HER2 fusion protein (CD1d-antitumor) is combined or not with OVA peptide/CpG vaccine. (biomedcentral.com)
  • 2008 Multiple studies show that this transactivation is influenced by the precise structure of glycolipid antigens which has enabled manipulation of immune responses with structural analogs of αGC (Venkataswamy and Porcelli 2010 For example derivatives of αGC containing truncated or unsaturated N-acyl chains induce responses in which cytokines typically associated with T helper-2 (Th2) cells predominate KM 11060 and transactivation of NK cells is limited (Yu et?al. (biotech-angels.com)
  • Our results demonstrate that simplexide, apart from activating iNKT cells, induces the production of cytokines and chemokines from human monocytes by direct interaction with CD1d. (cirn-na.com)
  • We feel this project is innovative because it will provide the vaccine community with mechanistic information when CD1d-binding adjuvants are combined with Alum adjuvant and give careful consideration to NKT cell- driven components of the immune response. (grantome.com)
  • We feel the project is significant because it will illuminate potential avenues for inclusion of CD1d-binding glycolipids in mixed adjuvant platforms. (grantome.com)
  • Altogether, our study in mice demonstrates that αGC/CD1d-antitumor fusion protein greatly increases the efficacy of a therapeutic CpG-based cancer vaccine, first as an adjuvant during T cell priming and second, as a therapeutic agent to redirect immune responses to the tumor site. (biomedcentral.com)
  • The Kronenberg lab focuses on understanding innate-like lymphocytes, mainly natural killer T (NKT) cells, a subset of T cells that recognizes glycolipids and is involved in a variety of immune responses including autoimmune, anti-tumoral responses and antimicrobial responses. (wikipedia.org)
  • Expanded Vδ3 T cells recognized CD1d but not CD1a, CD1b, or CD1c. (manchester.ac.uk)
  • The most well-defined antigen for iNKT cells is usually -galactosylceramide (-GalCer), a marine sponge-derived glycolipid that specifically targets iNKT cells and no other lymphocyte populations directly [9]. (sicollaborative.org)
  • A. Representative spleen sections from 3 mo old B6.TC (left) and B6 (right) mice stained with Moma-1-FITC, CD1d-PE and B220-PB. (bio-rad-antibodies.com)
  • Representative spleen sections from 10 mo old B6.TC (left) and B6 (right) mice stained with CD4-FITC, CD1d-PE and B220-PB. (bio-rad-antibodies.com)
  • Introduction Natural killer T (NKT) cells are a unique subset of CD1d-restricted T cells that provide a link between innate and adaptive immune responses. (sicollaborative.org)
  • Alterations in cellular metabolism modulate CD1d-mediated NKT-cell responses. (umaryland.edu)
  • Finally, the generation of short-lived plasmablasts MG-132 in vitro during natural or postimmune B-cell responses to TI antigens such as microbial carbohydrates and glycolipids involves multiple subsets of myeloid and plasmacytoid DCs, FDCs, epithelial cells, neutrophils, basophils, and mast cells, particularly in the MZ of the spleen and at mucosal sites. (pdgfrsignals.com)
  • 2010 In the current study we reassessed the presentation of various forms DUSP2 of αGC in?vivo to identify the predominant APCs involved in presentation of diverse glycolipid antigens. (biotech-angels.com)
  • Rapid development of a gamma interferon-secreting glycolipid/CD1d-specific V alpha 14(+) NK1.1(-) T-cell subset after bacterial infection. (mpg.de)
  • No. 553988, dashed line histogram) or with the FITC Rat Anti-Mouse CD1d antibody (Cat. (bdbiosciences.com)
  • No. 559871, for the purified antibody), suggesting a possible role for CD1d in mucosal immunity. (bdbiosciences.com)
  • Rat anti Mouse CD1d antibody, clone 1B1 ( MCA4700 ) used for immunofluorescence staining of mouse tissues. (bio-rad-antibodies.com)
  • Here we show that NKT cells recognized diacylglycerol -containing glycolipids from Streptococcus pneumoniae , the leading cause of community -acquired pneumonia , and group B Streptococcus , which causes neonatal sepsis and meningitis . (bvsalud.org)
  • GC) and delineate the mechanisms of action with a particular emphasis on CD1d-restricted Natural Killer T (NKT) cells and humoral immunity. (grantome.com)
  • The glycolipid response was dependent on vaccenic acid , which is present in low concentrations in mammalian cells . (bvsalud.org)
  • Thus, Vδ3 T cells are glycolipid-reactive T cells with distinct Ag specificities but functional similarities to NKT cells. (manchester.ac.uk)
  • 1997 it has been proposed that selective presentation by different cell types could account for variation in functional outcomes with different glycolipid antigens (Bezbradica et?al. (biotech-angels.com)
  • GC leads to CD1d/glycolipid presentation and a coordinated dNKT and iNKT- driven mixed Th1/Th2 response against vaccine antigens. (grantome.com)
  • Lysosomal recycling terminates CD1d-mediated presentation of short and polyunsaturated variants of the NKT cell lipid antigen alphaGalCer. (uchicago.edu)
  • Simplexide belongs to a novel class of glycolipids isolated from marine sponges and is structurally distinct from other immunologically active glycolipids. (cirn-na.com)
  • 2009 Because most cells of hematopoietic origin express CD1d (Brossay et?al. (biotech-angels.com)
  • MAb 1B1 detects CD1d at varying levels on most types of bone marrow and peripheral leukocytes and on epithelial, dendritic, and lymphoid cells in the thymus. (bdbiosciences.com)
  • The combined CD1d/iNKT antitumor therapy and CpG/peptide-based immunization leads to optimized expansion of NK and OVA-specific CD8 T cells (CTLs), likely resulting from the maturation of highly pro-inflammatory DCs as seen by a synergistic increase in serum IL-12. (biomedcentral.com)