Affinage

CD1D

Antigen-presenting glycoprotein CD1d · UniProt P15813

Length
335 aa
Mass
37.7 kDa
Annotated
2026-04-28
100 papers in source corpus 42 papers cited in narrative 42 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD1d is a non-polymorphic MHC class I-like glycoprotein that presents lipid and glycolipid antigens to NKT cells and γδ T cells, functioning as a central organizer of lipid-mediated adaptive immunity. Its hydrophobic binding groove accommodates diverse lipid antigens — including α-galactosylceramide, phosphatidylinositol mannosides, sulfatide, phosphatidylcholine, lysophosphatidylcholine, and cardiolipin — with two acyl chains buried in the A′ and F′ pockets and the polar headgroup exposed for TCR contact; lipid loading is initiated by microsomal triglyceride transfer protein (MTP) in the endoplasmic reticulum and refined by acid sphingomyelinase-mediated removal of non-stimulatory sphingomyelin in endosomes, while β2-microglobulin association is required for normal secretory trafficking (PMID:16002697, PMID:16314439, PMID:15107843, PMID:16087713, PMID:31636468, PMID:10092605). The invariant NKT TCR docks parallel to the CD1d binding cleft in a germline-encoded lock-and-key interaction dominated by the TCRα chain, with TCRβ CDR3 variability modulating autoreactivity and fine antigen specificity (PMID:17581592, PMID:21376640). Beyond antigen presentation, CD1d engagement on epithelial cells and hepatocytes triggers intrinsic signaling through a cytoplasmic tail–JAK2–STAT3 axis that induces IL-10 and anti-apoptotic effectors, conferring tissue-protective functions in the gut and liver (PMID:24717441, PMID:38438948).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1996 Medium

    The question of whether CD1d surface expression is dynamically regulated was answered by showing that IFN-γ transcriptionally upregulates CD1d on intestinal epithelial cells, establishing CD1d as a cytokine-responsive antigen-presenting molecule.

    Evidence Dose-response IFN-γ treatment of multiple IEC lines with RT-PCR and surface ELISA

    PMID:8760056

    Open questions at the time
    • Single lab; transcription factor mediating IFN-γ induction not identified
    • In vivo relevance of IEC CD1d upregulation not tested
  2. 1997 High

    Whether NKT cells use their TCR to specifically recognize CD1d (rather than other CD1 isoforms) was resolved by showing that Vα24+ T cells discriminate CD1d from CD1a/b/c in a TCR-dependent manner, establishing CD1d as the restricting element for invariant NKT cells.

    Evidence T cell clone stimulation assays with antibody blocking across CD1 family members

    PMID:9207002

    Open questions at the time
    • Nature of the endogenous ligand presented was unknown
    • Structural basis of CD1d selectivity unresolved
  3. 1999 High

    The biophysical basis of lipid antigen binding to CD1d was established by demonstrating direct, pH-independent binding of α-GalCer and other lipids to soluble CD1d, and by showing that β2-microglobulin is required for normal CD1d maturation through the secretory pathway.

    Evidence Surface plasmon resonance with soluble CD1d; pulse-chase metabolic labeling and endoglycosidase digestion of CD1d transfectants

    PMID:10092605 PMID:10523605

    Open questions at the time
    • Lipid-binding stoichiometry and groove architecture not yet visualized
    • Identity of physiological self-lipids unknown
  4. 2000 High

    Whether CD1d presents self-lipids (not just foreign glycolipids) was answered by showing that cellular phospholipids extracted from tumor cells stimulate NKT hybridomas via plate-bound CD1d, establishing self-lipid surveillance as a CD1d function.

    Evidence In vitro antigen presentation with plate-bound mCD1d loaded with purified phospholipids and tumor-derived lipid extracts

    PMID:10714687

    Open questions at the time
    • Specific self-lipid species not identified
    • Mechanism of self-lipid loading not addressed
  5. 2001 High

    The in vivo functional importance of CD1d intracellular trafficking was established by showing that the cytoplasmic tail tyrosine motif is essential for NKT cell development and antigen presentation despite normal surface CD1d levels.

    Evidence Knock-in mice with deleted cytoplasmic tail tyrosine motif, in vivo NKT cell phenotyping

    PMID:11731798

    Open questions at the time
    • The adaptor protein linking the tyrosine motif to endosomal sorting was not identified
    • Whether lipid exchange in endosomes requires this motif was untested
  6. 2004 High

    The mechanism of lipid loading onto nascent CD1d was identified: MTP in the ER associates with CD1d and is required for functional lipid antigen presentation, as shown by conditional MTP deletion in hepatocytes impairing NKT activation.

    Evidence Conditional Mttp knockout mice, co-immunoprecipitation of MTP–CD1d, NKT activation assays

    PMID:15107843

    Open questions at the time
    • Specificity of lipid species loaded by MTP onto CD1d was unclear
    • Whether MTP acts catalytically or as a scaffold was unresolved
  7. 2005 High

    Multiple structural and functional advances in 2004–2005 defined the CD1d lipid-binding groove architecture, confirmed MTP directly transfers phospholipids to CD1d in vitro, established that cortical thymocyte CD1d is sufficient for NKT selection, identified CD1d's role in post-selection NKT maturation, and revealed KSHV immune evasion via MIR-mediated ubiquitination of CD1d.

    Evidence Crystal structures of CD1d–sulfatide (1.9 Å) and CD1d–phosphatidylcholine (2.8 Å); in vitro MTP lipid transfer to recombinant CD1d; transgenic mice restricting CD1d to cortical thymocytes; adoptive transfer into CD1d-deficient hosts; MIR transfection with ubiquitination and surface expression assays

    PMID:15864354 PMID:16002697 PMID:16027237 PMID:16087713 PMID:16148122 PMID:16314439

    Open questions at the time
    • How endosomal lipid exchange enzymes (saposins) cooperate with CD1d was not structurally resolved
    • Whether MTP loads all self-lipids or a specific subset remained open
    • Full NKT TCR–CD1d docking geometry still unknown
  8. 2007 High

    The structural basis of NKT TCR recognition of CD1d was solved: the NKT TCR docks parallel to and at the extreme end of the CD1d cleft, with the germline-encoded TCRα chain making lock-and-key contact with CD1d–α-GalCer.

    Evidence X-ray crystallography of human NKT TCR–CD1d–α-GalCer ternary complex

    PMID:17581592

    Open questions at the time
    • How TCRβ chain variability modulates antigen specificity was not structurally resolved
    • Recognition of self-lipid antigens not yet crystallographically captured
  9. 2007 High

    CD1d on B cells was shown to be the direct mechanism of NKT cell help for humoral immunity, and IFN-β was found to post-transcriptionally upregulate CD1d protein synthesis during bacterial infection.

    Evidence B cell reconstitution of μMT mice with WT vs CD1d−/− B cells; metabolic labeling of DCs during Listeria infection with and without IFN-β

    PMID:17114455 PMID:18077787

    Open questions at the time
    • Signals downstream of NKT–B cell CD1d interaction for class switching were not mapped
    • Translational mechanism of IFN-β-induced CD1d synthesis not identified
  10. 2011 High

    Structural studies revealed how NKT TCR autoreactivity arises (CDR3β hydrophobic contacts with CD1d), how diverse self-lipids including cardiolipin occupy the groove with partial solvent exposure, and mass spectrometry identified the full self-lipid repertoire of CD1d.

    Evidence Crystal structures of autoreactive NKT TCR–PI–CD1d (2.3 Å) and CD1d–cardiolipin (2.3 Å); MS of purified CD1d lipid content

    PMID:21376640 PMID:21389252 PMID:21900247

    Open questions at the time
    • Functional hierarchy among self-lipids for NKT selection not established
    • Whether cardiolipin-reactive γδ T cells contribute to mitochondrial damage sensing was unknown
  11. 2012 High

    CD1d was shown to also restrict γδ T cells (Vδ1 TCRs bind CD1d–sulfatide), and structural analysis of CD1d–lysophosphatidylcholine revealed an induced-fit mechanism where TCR binding stabilizes a conformational shift in the α1 helix.

    Evidence Recombinant Vδ1 TCR binding to CD1d–sulfatide tetramers; crystal structures of CD1d–LPC ± TCR

    PMID:22395072 PMID:22829134

    Open questions at the time
    • Physiological role of γδ T cell CD1d restriction in vivo uncharacterized
    • Whether induced-fit applies to all self-lipid antigens is unknown
  12. 2014 High

    A cell-intrinsic signaling function of CD1d was discovered: CD1d crosslinking on intestinal epithelial cells activates STAT3, inducing IL-10 and a protective feedback loop; IEC-specific deletion of CD1d, IL-10, or MTP causes NKT-mediated colitis.

    Evidence IEC-specific conditional deletion of CD1d, IL-10, and MTP; STAT3 phosphorylation assays; colitis models

    PMID:24717441

    Open questions at the time
    • The ligand or cell type that crosslinks CD1d on IECs in vivo was not identified
    • Proximal kinase linking CD1d cytoplasmic tail to STAT3 in IECs not determined at this time
  13. 2015 High

    HSV-1 immune evasion via CD1d was mechanistically resolved: viral kinase US3 phosphorylates KIF3A at Ser687, blocking kinesin-dependent CD1d recycling to the surface.

    Evidence In vitro kinase assay, mass spectrometry of KIF3A, Ser687 mutagenesis abolishing US3-mediated CD1d downregulation

    PMID:25878107

    Open questions at the time
    • Whether KIF3A-dependent transport applies to CD1d recycling in uninfected cells was not tested
    • Other kinesin family members potentially involved not excluded
  14. 2019 High

    The role of lipid editing in CD1d function was established: acid sphingomyelinase removes non-stimulatory sphingomyelin from CD1d; ASM deficiency in mice and Niemann-Pick patients causes sphingomyelin accumulation in CD1d, impaired antigen presentation, and iNKT cell deficiency.

    Evidence ASM knockout mice, human Niemann-Pick disease patient iNKT quantification, pharmacological ASM rescue

    PMID:31636468

    Open questions at the time
    • Whether other lipid hydrolases contribute to CD1d editing was not tested
    • The endosomal compartment where ASM acts on CD1d-bound sphingomyelin was not localized
  15. 2023 High

    The proximal signaling mechanism of CD1d in hepatocytes was identified: CD1d crosslinking induces cytoplasmic tail tyrosine phosphorylation, recruiting JAK2 which activates STAT3 to upregulate anti-apoptotic Bcl-xL/Mcl-1, protecting against hepatocyte apoptosis in NASH.

    Evidence Anti-CD1d antibody crosslinking, phosphorylation assays, hepatocyte-specific overexpression/knockdown, in vivo NASH models

    PMID:38438948

    Open questions at the time
    • The kinase that phosphorylates the CD1d tail tyrosine upstream of JAK2 recruitment is unknown
    • Whether this signaling pathway operates in other CD1d-expressing non-immune cells is untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include: the identity of the in vivo ligand(s) and cell type that crosslink CD1d on non-immune cells to activate its intrinsic signaling; the structural basis by which saposins mediate lipid exchange in endosomes; and the rules governing the self-lipid repertoire that shapes NKT cell selection versus peripheral activation.
  • No structural data on saposin–CD1d interaction
  • In vivo CD1d crosslinking ligand on non-immune cells unidentified
  • Quantitative rules linking self-lipid repertoire to NKT thymic selection thresholds unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 9 GO:0048018 receptor ligand activity 3 GO:0060089 molecular transducer activity 2
Localization
GO:0005886 plasma membrane 6 GO:0005783 endoplasmic reticulum 4 GO:0005768 endosome 2 GO:0005576 extracellular region 1
Pathway
R-HSA-168256 Immune System 7 R-HSA-1643685 Disease 3 R-HSA-162582 Signal Transduction 2
Partners
B2MJAK2KIF3AMTTPSMPD1STAT3
Complex memberships
CD1d–β2-microglobulin heterodimer

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 Crystal structure of human NKT TCR in complex with CD1d bound to alpha-galactosylceramide revealed that the NKT TCR docks parallel to, and at the extreme end of, the CD1d binding cleft in a lock-and-key interaction with the lipid antigen, with the conserved NKT TCR alpha-chain mediating germline-encoded recognition of CD1d. X-ray crystallography of NKT TCR–CD1d–alpha-GalCer ternary complex Nature High 17581592
1997 Human invariant Valpha24+ CD4-CD8- T cells recognize CD1d in a TCR-mediated manner, discriminating between CD1d and other CD1 family members; recognition was not dependent on an endosomal targeting motif in the CD1d cytoplasmic tail. T cell clone stimulation assays, antibody blocking, CD1d family member discrimination The Journal of experimental medicine High 9207002
2000 Mouse CD1d presents cellular phospholipids as self-antigens to NKT cell hybridomas; lipid extract from tumor cells and purified phospholipids stimulated NKT hybridomas via plate-bound mCD1d. In vitro antigen presentation assay with plate-bound mCD1d, lipid extract fractionation, purified phospholipid stimulation Immunity High 10714687
2004 Mycobacterial phosphatidylinositol mannoside (PIM) binds CD1d and activates NKT cells; structural requirements for CD1d binding include two acyl chains and a polar head group; PIM-loaded CD1d tetramers identify a subpopulation of NKT cells. CD1d-binding assays, T cell activation assays, CD1d tetramer staining Proceedings of the National Academy of Sciences of the United States of America High 15243159
2001 The CD1d cytoplasmic tail tyrosine-based motif is essential in vivo for intracellular trafficking, antigen presentation, and NKT cell development; knock-in mice with deleted cytoplasmic tail showed multiple and selective abnormalities despite adequate surface CD1d expression. Knock-in mouse (homologous recombination deleting cytoplasmic tail tyrosine motif), in vivo NKT cell development and antigen presentation analysis Nature immunology High 11731798
2005 Crystal structure of mouse CD1d bound to cis-tetracosenoyl sulfatide at 1.9 Å resolution showed the fatty acid chain occupying the A' pocket and sphingosine chain filling the F' pocket; precise hydrogen bond network orients the ceramide backbone; the sulfated galactose headgroup is highly exposed for TCR contact. X-ray crystallography at 1.9 Å resolution The Journal of experimental medicine High 16314439
2004 Microsomal triglyceride transfer protein (MTP) associates with CD1d in hepatocytes; conditional deletion of Mttp in hepatocytes impairs NKT cell activation and redistributes CD1d expression, demonstrating MTP's role in lipid loading onto CD1d in the endoplasmic reticulum. Conditional knockout mice, co-immunoprecipitation, in vitro NKT cell activation assays, gene silencing Nature medicine High 15107843
2005 Purified MTP directly transfers phospholipids (but not triglycerides) to recombinant CD1d in vitro; MTP chemical inhibition reduces CD1d-mediated antigen presentation of alpha-GalCer and endogenous antigens without affecting MHC class II presentation, indicating MTP loads endogenous lipids onto nascent CD1d in the ER. In vitro lipid transfer assay with purified MTP and recombinant CD1d, chemical inhibition, siRNA knockdown, antigen presentation assays The Journal of experimental medicine High 16087713
1999 Soluble mouse and human CD1d molecules bind alpha-GalCer at neutral pH as measured by surface plasmon resonance; CD1d can also bind beta-GalCer and phosphatidylethanolamine; orientation of the galactose headgroup is more important for TCR contact than CD1d binding per se. Surface plasmon resonance, plate-bound soluble CD1d antigen presentation assays The Journal of experimental medicine High 10523605
2006 PPARgamma induces expression of retinol and retinal metabolizing enzymes (RDH10, RALDH2) in dendritic cells, increasing intracellular all-trans retinoic acid (ATRA), which activates RARalpha and directly up-regulates CD1d expression and iNKT cell activation. Gene expression analysis, enzyme activity assays, RARalpha activation assays, iNKT cell activation The Journal of experimental medicine High 16982809
2005 Crystal structure of mouse CD1d bound to phosphatidylcholine at 2.8 Å resolution revealed interactions between lipid acyl chains and the CD1d binding groove; headgroup orientation toward C-terminus of alpha1 helix provides structural basis for invariant NKT cell Valpha chain bias. X-ray crystallography at 2.8 Å resolution Journal of immunology High 16002697
2006 Crystal structure of mouse CD1d in complex with mycobacterial dipalmitoyl-PIM2 at 2.6 Å resolution revealed a specific hydrogen-bonding network between PIM2 and CD1d residues (Asp153, Thr156, Ser76, Arg79) orienting the complex headgroup above the A' pocket; specificity for additional mannoses conferred by Thr159. X-ray crystallography at 2.6 Å resolution Journal of immunology High 16982895
2011 Crystal structure of an autoreactive NKT TCR–phosphatidylinositol–CD1d complex at 2.3 Å resolution revealed that NKT TCR autoreactivity is mediated by unique hydrophobic sequences in the non-germline-encoded CDR3β loop promoting self-association with CD1d, while germline-encoded recognition of CD1d is conserved across self and foreign antigens. X-ray crystallography at 2.3 Å resolution, binding studies with natural self-antigens Immunity High 21376640
2011 Cardiolipin (CL) binds to murine CD1d with two alkyl chains buried in the CD1d binding groove and two chains exposed to solvent (crystal structure at 2.3 Å); CD1d-CL complexes stimulate splenic and hepatic γδ T cells to produce IFN-γ and RANTES in a CD1d-restricted manner. X-ray crystallography at 2.3 Å resolution, lipid loading assay, in vitro and in vivo γδ T cell stimulation assays Journal of immunology High 21389252
2005 CD1d expressed on cortical thymocytes is both necessary and sufficient for NKT cell thymic selection, expansion, acquisition of memory phenotype, and cytokine production; restricting CD1d expression to cortical thymocytes in transgenic/chimeric mice was sufficient for these differentiation events. Transgenic and chimeric mouse approach restricting CD1d expression to cortical thymocytes The Journal of experimental medicine High 16027237
2005 CD1d is required for post-selection NKT cell maturation (acquisition of NK1.1); immature NK1.1- NKT cells fail to fully mature when transferred to a CD1d-deficient environment, but long-term survival of NKT cells is largely CD1d-independent. Adoptive transfer of NKT cells into CD1d-deficient recipients, phenotypic analysis Journal of immunology High 16148122
2005 CD1d evasion by KSHV is caused by the viral MIR proteins, which ubiquitinate the CD1d alpha-chain on a unique lysine in its cytoplasmic tail, triggering endocytosis and loss of surface CD1d without accelerated lysosomal degradation; this reduces CD1d-restricted T cell activation. Transfection of MIR proteins, ubiquitination assay, surface expression analysis, functional T cell activation assay The Journal of clinical investigation High 15864354
2015 HSV-1 protein kinase US3 phosphorylates cellular kinesin motor protein KIF3A predominantly at serine 687, impairing CD1d recycling to the cell surface; ablation of this phosphorylation site abolished US3-mediated CD1d downregulation, identifying KIF3A as essential for CD1d surface expression. In vitro kinase assay, mass spectrometry of purified KIF3A, mutagenesis of phosphorylation site, surface CD1d expression analysis Journal of virology High 25878107
2014 CD1d crosslinking on intestinal epithelial cells activates STAT3 and STAT3-dependent transcription of IL-10, HSP110, and CD1d itself; IEC-specific deletion of IL-10, CD1d, or MTP causes severe NKT-cell-mediated colitis, revealing a CD1d–STAT3–IL-10 protective epithelial signaling pathway. IEC-specific conditional deletion, STAT3 activation assays, cytokine measurements, colitis models Nature High 24717441
2023 Anti-CD1d crosslinking on hepatocytes induces tyrosine phosphorylation of the CD1d cytoplasmic tail, recruiting and phosphorylating JAK2, which activates STAT3 to increase anti-apoptotic effectors (Bcl-xL, Mcl-1) and decrease pro-apoptotic signaling; this CD1d–JAK2–STAT3 axis protects against hepatocyte apoptosis in NASH. Anti-CD1d antibody crosslinking, phosphorylation assays, hepatocyte-specific overexpression and knockdown, in vivo liver injury models Journal of hepatology High 38438948
1999 In the absence of beta2-microglobulin, CD1d is expressed on the cell surface as an endoglycosidase-H-sensitive 45-kDa glycoprotein that fails to acquire endoglycosidase-H resistance, indicating that beta2m association is required for CD1d to transit normally through the secretory pathway and acquire complex glycosylation. CD1d transfectants, pulse-chase metabolic labeling, endoglycosidase digestion, immunoprecipitation The Journal of biological chemistry High 10092605
2003 CD1d expression on cardiac myocytes is upregulated by myocarditic CVB3 but not by non-myocarditic variants; Vγ4+ T cells kill CVB3-infected myocytes via CD1d in a cytotoxicity assay blocked by anti-CD1d antibody; CD1d-deficient mice do not develop CVB3-induced myocarditis. CD1d KO mice, in vitro cytotoxicity assays with anti-CD1d blocking antibody, flow cytometry of infected myocytes Journal of immunology Medium 12626572
2008 CD1d engagement by anti-CD1d monoclonal antibodies on myeloma cells with restored CD1d expression induces caspase-independent cell death associated with Bax overexpression and mitochondrial membrane potential loss; this requires the CD1d cytoplasmic tail but not the tyrosine residue critical for lysosomal sorting. Anti-CD1d mAb crosslinking, apoptosis assays (Bax expression, mitochondrial potential), cytoplasmic tail mutants Blood Medium 19056691
2012 Human Vδ1 γδ TCRs bind recombinant CD1d-sulfatide complexes in a sulfatide-specific manner as demonstrated by recombinant TCR binding to CD1d tetramers, providing the first direct demonstration of MHC-like-restricted antigen-specific recognition by γδ TCRs. CD1d-sulfatide tetramer binding, recombinant TCR production and binding assay, MACS enrichment European journal of immunology High 22829134
2012 Lysophosphatidylcholine (LPC) presented by human CD1d adopts an altered CD1d conformation with a shifted alpha1 helix and open A' pocket; iNKT TCR binding to CD1d-LPC requires a 7-Å displacement of the LPC headgroup but stabilizes the CD1d-LPC complex in a closed conformation. X-ray crystallography, biophysical binding assays The EMBO journal High 22395072
2011 Mass spectrometry analysis of lipids specifically loaded into purified CD1d proteins identified nine novel self-lipids presented by CD1d, with enrichment of particular lipid motifs, indicating CD1d surveys the endoplasmic reticulum, Golgi, and/or secretory compartments. Mass spectrometry of purified CD1d protein lipid content with rigorous controls The Journal of biological chemistry High 21900247
2019 Acid sphingomyelinase (ASM) degrades sphingomyelin, a non-activating lipid that competes for CD1d binding; ASM deficiency leads to sphingomyelin accumulation in CD1d, diminished antigen presentation, defective iNKT cell thymic selection, and decreased iNKT cell numbers in both mice and humans with Niemann-Pick disease. ASM knockout mice, human Niemann-Pick disease patient analysis, pharmacological ASM administration, iNKT cell quantification Nature immunology High 31636468
2006 IFN-beta is required for up-regulation of CD1d in Listeria monocytogenes-infected dendritic cells and macrophages; unlike MHC class I, this up-regulation is not transcriptionally regulated but results from increased de novo CD1d protein synthesis, leading to enhanced iNKT cell activation. In vivo infection model, in vitro IFN-beta treatment, confocal microscopy, metabolic labeling, RT-PCR, functional NKT activation assay Journal of immunology High 17114455
1996 IFN-gamma up-regulates CD1d mRNA and surface protein expression on intestinal epithelial cell lines in a dose- and time-dependent, cytokine-specific manner. Cell surface ELISA, RT-PCR, cytokine dose-response experiments on multiple epithelial cell lines The American journal of physiology Medium 8760056
2003 Intestinal heat shock protein 110 (Hsp110) present in intestinal luminal contents induces CD1d surface expression on intestinal epithelial cells, representing a novel autocrine pathway of CD1d regulation. RT-PCR, confocal microscopy, cell surface ELISA, Western blot, biochemical fractionation and identification of Hsp110 The Journal of clinical investigation Medium 12952923
2017 Hepatocyte-specific loss of MTP impairs CD1d function and increases hepatic iNKT cell numbers due to altered iNKT cell apoptosis; hepatocyte-specific CD1d deletion produces similar findings, demonstrating that hepatocyte CD1d controls local liver iNKT cell homeostasis. Hepatocyte-specific conditional KO mice for both MTP and CD1d, apoptosis assays, hepatitis models Proceedings of the National Academy of Sciences of the United States of America High 28893990
2007 In fatty livers, ER stress reduces the pool of CD1d at the plasma membrane of hepatocytes (despite normal CD1d mRNA), impairing their ability to activate CD1d-restricted T cells; tunicamycin-induced ER stress reproduces these defects in lean mice. Flow cytometry, in vitro T cell activation assays, tunicamycin treatment of cultured hepatocytes and lean mice Laboratory investigation Medium 17307300
2015 miR-155 directly targets the 3'-UTR of CD1d mRNA upon TLR9 activation in B cells, reducing CD1d protein and impairing antigen presentation to iNKT cells; Ets-1 directly regulates CD1d gene transcription. 3'-UTR reporter assays, miR-155 overexpression/inhibition, TLR9 stimulation, iNKT cell activation assay European journal of immunology Medium 25929465
2016 HDAC2 binds to the CD1D promoter; HDAC2 knockdown in tumor cells increases CD1d mRNA and surface expression and enhances CD1d-mediated NKT cell antigen presentation; pan-HDACi treatment also inhibits STAT3, which reduces IL-10 secretion that otherwise inhibits CD1d-mediated presentation. ChIP (HDAC2 on CD1D promoter), siRNA knockdown, surface CD1d expression, NKT cell activation assay Cancer immunology, immunotherapy Medium 27614429
2010 DPPE-PEG, a CD1d-binding lipid antagonist, competes with alpha-GalCer for binding to CD1d and completely inhibits alpha-GalCer-induced ERK phosphorylation in iNKT cells, thereby blocking TCR signaling and preventing iNKT cell-mediated airway hyperreactivity. CD1d competitive binding assay, ERK phosphorylation assay in iNKT cells, mouse model of airway hyperreactivity Journal of immunology Medium 20083656
2011 Galactose-modified iNKT cell agonists bind CD1d via an induced-fit mechanism using an aromatic substitution as a third anchor in addition to the two lipid chains, stabilizing CD1d binding and driving superior Th1 cytokine responses and tumor protection. Equilibrium lipid binding assays, crystal structure analysis, iNKT cell cytokine assays, in vivo tumor protection model The EMBO journal High 21552205
2017 A 'TCR trap' method that captures lipids within CD1d–lipid–TCR complexes identified alpha-linked monohexosylceramides from cow's milk as specific lipid antigens recognized by iNKT cells, as confirmed by mass spectrometry fragmentation patterns. TCR trap immunoprecipitation of CD1d-lipid-TCR complex followed by mass spectrometry Proceedings of the National Academy of Sciences of the United States of America High 28716901
2007 CD1d-expressing B cells are absolutely required for NKT-enhanced antibody responses; reconstituting B cell-deficient mice with CD1d-/- B cells abolished NKT-enhanced Ab responses, demonstrating that direct CD1d presentation by B cells is the mechanism of NKT cell help for humoral immunity. B cell reconstitution of microMT mice with wild-type or CD1d-/- B cells, immunization and antibody measurement Blood High 18077787
2016 Adipocyte-specific CD1d deletion in mice reduces visceral adipose tissue mass and improves insulin sensitivity on high-fat diet, decreases NKT cell activation and IFN-γ production, and blunts macrophage recruitment into adipose tissue; 3T3-L1 adipocytes present endogenous ligands to NKT cells via CD1d leading to IFN-γ production. Adipocyte-specific CD1d conditional KO mice, high-fat diet model, in vitro NKT cell stimulation by adipocytes, metabolic measurements Scientific reports High 27329323
2024 The amine headgroups of ionizable lipids in lipid nanoparticles bind directly to CD1d (and TLR4) and promote lipid-raft formation, driving NKT cell-mediated immune responses including type-1 T-helper-cell-biased cytokine production. Binding assays to CD1d, lipid-raft formation assays, immunological profiling of LNP-immunized mice Nature biomedical engineering Medium 39363106
2016 A hydrophobic patch formed by TCRα-TCRβ pairing is required for NKT TCR recognition of CD1d but not MHC; partial disruption of this patch selectively allowed CD1d recognition while altering NKT cell development, resulting in accumulation of adipose-tissue-resident NKT cells. Molecular modeling, mutagenesis of TCR hydrophobic patch, transgenic mouse models, flow cytometry of tissue NKT cells Nature immunology High 27869818
2009 CD1d polymorphisms in wild-derived mouse strains affect the presentation of endogenous and exogenous lipid ligands to both type I and type II NKT cells, and CD1d polymorphisms influence thymic selection of type I NKT cells and induce allogeneic T cell responses. Congenic mice with identified CD1d alleles, antigen presentation assays, thymic NKT cell development analysis Proceedings of the National Academy of Sciences of the United States of America Medium 19179286

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 CD1d-lipid-antigen recognition by the semi-invariant NKT T-cell receptor. Nature 477 17581592
1997 Requirements for CD1d recognition by human invariant Valpha24+ CD4-CD8- T cells. The Journal of experimental medicine 419 9207002
2012 Recognition of CD1d-restricted antigens by natural killer T cells. Nature reviews. Immunology 369 23154222
2000 Murine CD1d-restricted T cell recognition of cellular lipids. Immunity 362 10714687
2004 Mycobacterial phosphatidylinositol mannoside is a natural antigen for CD1d-restricted T cells. Proceedings of the National Academy of Sciences of the United States of America 287 15243159
1999 Tissue-specific segregation of CD1d-dependent and CD1d-independent NK T cells. Journal of immunology (Baltimore, Md. : 1950) 239 10352254
2001 Activation of CD1d-restricted T cells protects NOD mice from developing diabetes by regulating dendritic cell subsets. Proceedings of the National Academy of Sciences of the United States of America 215 11707602
2003 CD1d-restricted NKT cells express a chemokine receptor profile indicative of Th1-type inflammatory homing cells. Journal of immunology (Baltimore, Md. : 1950) 184 12928408
2014 Protective mucosal immunity mediated by epithelial CD1d and IL-10. Nature 174 24717441
2001 Multiple defects in antigen presentation and T cell development by mice expressing cytoplasmic tail-truncated CD1d. Nature immunology 161 11731798
2005 Structural basis for CD1d presentation of a sulfatide derived from myelin and its implications for autoimmunity. The Journal of experimental medicine 159 16314439
2006 PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. The Journal of experimental medicine 157 16982809
2000 CD1d structure and regulation on human thymocytes, peripheral blood T cells, B cells and monocytes. Immunology 156 10809957
2000 Overexpression of CD1d by keratinocytes in psoriasis and CD1d-dependent IFN-gamma production by NK-T cells. Journal of immunology (Baltimore, Md. : 1950) 156 11034419
2012 The majority of CD1d-sulfatide-specific T cells in human blood use a semiinvariant Vδ1 TCR. European journal of immunology 154 22829134
2010 Design of a potent CD1d-binding NKT cell ligand as a vaccine adjuvant. Proceedings of the National Academy of Sciences of the United States of America 150 20616071
2005 Regulation of CD1d expression and function by a herpesvirus infection. The Journal of clinical investigation 147 15864354
2004 CD1d function is regulated by microsomal triglyceride transfer protein. Nature medicine 137 15107843
2001 The mouse CD1d-restricted repertoire is dominated by a few autoreactive T cell receptor families. The Journal of experimental medicine 131 11304550
2005 Microsomal triglyceride transfer protein lipidation and control of CD1d on antigen-presenting cells. The Journal of experimental medicine 127 16087713
1999 Binding and antigen presentation of ceramide-containing glycolipids by soluble mouse and human CD1d molecules. The Journal of experimental medicine 125 10523605
2005 Expansion and long-range differentiation of the NKT cell lineage in mice expressing CD1d exclusively on cortical thymocytes. The Journal of experimental medicine 123 16027237
2001 CD1d-reactive T-cell activation leads to amelioration of disease caused by diabetogenic encephalomyocarditis virus. Journal of leukocyte biology 118 11358978
2011 A molecular basis for NKT cell recognition of CD1d-self-antigen. Immunity 116 21376640
1993 CD1d is involved in T cell-intestinal epithelial cell interactions. The Journal of experimental medicine 114 7688787
2006 Design of natural killer T cell activators: structure and function of a microbial glycosphingolipid bound to mouse CD1d. Proceedings of the National Academy of Sciences of the United States of America 110 16537470
2006 CD1d- and MR1-restricted invariant T cells: of mice and men. Current opinion in immunology 109 16870416
2011 Cardiolipin binds to CD1d and stimulates CD1d-restricted γδ T cells in the normal murine repertoire. Journal of immunology (Baltimore, Md. : 1950) 107 21389252
2005 The diverse functions of CD1d-restricted NKT cells and their potential for immunotherapy. Immunology letters 107 16083968
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