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  • CD1A
  • The human CD1 gene family is composed of five nonpolymorphic genes ( CD1A , CD1B , CD1C , CD1D , and CD1E ) ( 9 ), whereas mice express only CD1d molecules. (pnas.org)
  • Humans express five family members (CD1a-e) that can be grouped into three groups based on sequence similarity: group 1 (CD1a-c), group 2 (CD1d), and group 3 (CD1e) ( 5 , 6 ). (pnas.org)
  • Crystal structures of human CD1a, b, and d, as well as mouse CD1d, without loading specific antigens, or in complex with different glycolipids or lipopeptides, have been extensively reviewed elsewhere ( 7 ⇓ ⇓ - 10 ). (pnas.org)
  • ligand
  • Currently, the natural ligand(s) for CD1d-restricted NK T cells is unknown, although phosphoinositol-containing compounds have been suggested to be natural ligands for some of these cells ( 13 )( 14 )( 15 ). (rupress.org)
  • mice
  • Mice express only CD1d. (pnas.org)
  • GD3-reactive NKT cells were detected among splenocytes of immunized mice at frequencies of approximately 1:2000 both by ELISPOT and GD3-loaded mouse CD1d tetramer analysis. (nih.gov)
  • They were CD1d restricted in that reactivity was abrogated when APCs were blocked with anti-CD1d monoclonal antibody before being loaded with GD3 or when APCs from CD1d knockout mice were used. (nih.gov)
  • We have explored the role of CD1d-restricted NKT cells in atherosclerosis by using apolipoprotein E-deficient (apoE-/-) mice, a hypercholesterolemic mouse model that develops atherosclerosis. (nih.gov)
  • ApoE-/- mice crossed with CD1d-/- (CD1d-/-apoE-/-) mice exhibited a 25% decrease in lesion size compared with apoE-/- mice. (nih.gov)
  • Administration of alpha-galactosylceramide, a synthetic glycolipid that activates NKT cells via CD1d, induced a 50% increase in lesion size in apoE-/- mice, whereas it did not affect lesion size in apoE-/-CD1d-/- mice. (nih.gov)
  • 5-wk-old female apoE−/− and apoE−/−CD1d−/− mice were injected twice a week for 10 wk with αGalCer or PBS and killed 48 h after the last injection (n = 12 for each group). (nih.gov)
  • b) Lesion size at every 100 μm for the first 600 μm of the aortic root in apoE−/− and apoE−/−CD1d−/− mice. (nih.gov)
  • In apoE−/− CD1d−/− mice, αGalCer did not affect lesion size (Fig. 1, a and c), demonstrating that the effect of αGalCer on atherosclerosis depends on CD1d. (nih.gov)
  • tetramers
  • Here we show that tetramers of mouse CD1d loaded with α-GalCer are a sensitive and highly specific reagent for identifying Vα14 + NK T cells. (rupress.org)
  • Tetramers have been used widely to obtain a detailed analysis of the distribution and frequency of conventional CD4 + and CD8 + antigen-specific T cells during a variety of immune responses. (rupress.org)
  • Availability of α-GalCer/CD1d tetramers opened up new avenues of NKT cell research and laid the foundation for important findings in the field of immunoregulation. (frontiersin.org)
  • iNKT cell
  • Recently, a different category of glycolipids, α-galactosyl diacylglycerolipids (α-GalDAG), have been identified as novel iNKT cell antigens. (pnas.org)
  • Formation of larger nanoclusters occurs in the absence of interactions between CD1d cytosolic tail and the actin cytoskeleton and correlates with enhanced iNKT cell activation. (ox.ac.uk)
  • Overall, these results define a previously unidentified mechanism that modulates iNKT cell autoreactivity based on the tight control by the APC cytoskeleton of the sizes and densities of endogenous antigen-loaded CD1d nanoclusters. (ox.ac.uk)
  • Given the importance of human immune responses, we conducted a human-mouse cross-species analysis of iNKT-cell activation by iGb3-CD1d. (biomedsearch.com)
  • Here we show that human and mouse iNKT cells were both able to recognise iGb3 presented by mouse CD1d (mCD1d), but not human CD1d (hCD1d), as iGb3-hCD1d was unable to support cognate interactions with the iNKT-cell TCRs tested in this study. (biomedsearch.com)
  • In conclusion, our data indicate that iGb3 is unlikely to be a major antigen in human iNKT-cell biology. (biomedsearch.com)
  • Cytokines
  • Curiously, tetramer-positive thymocytes do not rapidly synthesize cytokines, nor do they undergo decreases in cell number after lipid antigen stimulation, although they express equivalent TCR levels. (rupress.org)
  • CD1d-dependent NK T cells are believed to be involved in the regulation of immune responses as a result of their potent ability to secrete cytokines. (rupress.org)
  • recognize
  • As antibodies are designed to specifically recognize and eliminate invading antigens, they are effective weapons used by the immune system to combat infection. (pnas.org)
  • Here we sought to test the hypothesis that B cell lymphomas use epigenetic mechanisms to dysregulate CD1d-mediated antigen processing and presentation leading to a functional impairment in the ability of NKT cells to recognize tumors. (biomedcentral.com)
  • reactivity
  • However, NK T cell reactivity to CD1d is greatly augmented by the glycosphingolipid α-galactosylceramide (α-GalCer) ( 16 ), obtained from an extract of the marine sponge Agelas mauritanius . (rupress.org)
  • Gene
  • Ternary structures of TRBV6-1, TRBV6-4, and TRBV20(+) MAIT TCRs in complex with MR1 bound to a potent riboflavin-based antigen (Ag) showed how variations in TRBV gene usage exclusively impacted on MR1 contacts within a consensus MAIT TCR-MR1 footprint. (jove.com)
  • TCR gene therapy allows for the mass redirection of T-cells against a defined antigen while high affinity TCR engineering allows for the creation of a new class of soluble drugs. (frontiersin.org)
  • tetramer
  • Type I NKT cells are reactive to the marine sponge-derived glycolipid α-galactosylceramide (α-GalCer) ( 8 ), which forms a stable α-GalCer/CD1d tetramer reagent that can be used for detection of type I NKT cells ( 9 , 10 ). (frontiersin.org)
  • complexes
  • Since the engagement of the T cell receptor (TCR) by CD1d-antigen complexes is a fundamental requirement of NKT cell activation, antigen: CD1d-Ig complexes provide a reliable method to isolate, activate, and expand effector NKT cell populations. (jove.com)
  • chains
  • CD1d also can bind nonantigenic lipids, however, but unexpectedly, mouse CD1d orients the two aliphatic chains of a nonantigenic lipid rotated 180°, causing a dramatic repositioning of the exposed sugar. (pnas.org)
  • intracellular
  • Specific antigen engagement initiates two BCR-mediated processes: the transmission of intracellular signals regulating entry into cell cycle ( 2 , 3 ) and antigen internalization before its processing and presentation in association with MHC to specific T cells ( 4 ). (pnas.org)
  • reactive
  • In contrast, type II NKT cells are not reactive to α-GalCer ( 11 , 12 ), instead they are thought to make up an oligoclonal population that recognizes a diverse repertoire of lipid antigens ( 5 , 7 , 13 ). (frontiersin.org)
  • activation
  • Second, NK1.1 + T cells may downregulate the NK1.1 marker upon activation ( 24 ), making it difficult to follow these cells once they have encountered antigen. (rupress.org)
  • In contrast, treatment with the more selective HDACi, MC1568, resulted in an increase in CD1d-mediated NKT cell activation, but did not enhance antigen presentation by HLA-DR4. (biomedcentral.com)
  • CD1d-dependent activation of NKT cells aggravates atherosclerosis. (nih.gov)
  • These results show that activation of CD1d-restricted NKT cells exacerbates atherosclerosis. (nih.gov)
  • cell
  • A major group of natural killer (NK) T cells express an invariant Vα14 + T cell receptor (TCR) specific for the lipoglycan α-galactosylceramide (α-GalCer), which is presented by CD1d. (rupress.org)
  • To assess the functional outcomes of epigenetic modulation, murine and human B cell lymphomas were pretreated with HDAC inhibitors and then we assessed their ability to process and present antigen. (biomedcentral.com)
  • The expression of CD1d and GD2 on neuroblastoma (NB) cell lines. (nih.gov)
  • a) The surface CD1d expression levels of various NB cell lines are shown. (nih.gov)
  • b) The CD1d expression levels of cell lines from hematological malignancies are shown as positive controls. (nih.gov)
  • As previously described,23 CD1d was expressed on hematopoietic cells, such as Jurkat and THP‐1 cells (Fig. 1b), but it was not expressed on the surface of NB cell lines (Fig. 1a). (nih.gov)
  • However, NKT cell based-immunotherapy has been limited by the use of autologous antigen presenting cells and the quantity and quality of these stimulator cells can vary substantially. (jove.com)
  • proteins
  • Many hematologic malignancies express CD1d and the co-stimulatory proteins needed to induce anti-tumor responses by NKT cells, yet most tumors are poorly immunogenic. (biomedcentral.com)