Affinage

CD1B

T-cell surface glycoprotein CD1b · UniProt P29016

Length
333 aa
Mass
36.9 kDa
Annotated
2026-04-28
100 papers in source corpus 31 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD1b is a β2-microglobulin-associated, MHC class I-like glycoprotein that presents lipid and glycolipid antigens to αβ and γδ T cells, functioning as a central mediator of lipid-based immune surveillance against mycobacteria and other pathogens. CD1b assembles with phosphatidylinositol and ER chaperones (calnexin, calreticulin), transits to the cell surface, and is internalized via AP-2/clathrin-dependent endocytosis to accumulate in lysosomal MHC class II compartments, where pH-dependent ionic tethers (D60, E62) open the antigen-binding groove for lipid loading assisted by saposin C and CD1e (PMID:11847129, PMID:18538591, PMID:14716313, PMID:22782895). Its unusually large hydrophobic groove (~2,200 ų) accommodates one or two lipid chains—including mycobacterial glucose monomycolate, mycolic acids, diacylsulfoglycolipids, lipoarabinomannan, and self-phospholipids—using endogenous scaffold lipids to fill unoccupied volume, while exposing polar headgroups or phosphate moieties for TCR contact (PMID:22087000, PMID:37725977, PMID:30610190). Conserved GEM T cells bearing TRAV1-2/TRAJ9 α-chains dock centrally above CD1b to grip mycobacterial glucose moieties, while autoreactive T cells recognize self-phospholipids through a lateral escape channel mechanism, collectively enabling CD1b-dependent T cell activation, IFN-γ production, and dendritic cell maturation (PMID:27807341, PMID:30610190, PMID:12415264).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1995 High

    Establishing that CD1b functions as a lipid antigen-presenting molecule resolved a longstanding question about how non-peptide microbial products are displayed to T cells; CD1b was shown to present mycobacterial lipoarabinomannan to αβ T cells in an endosomal acidification-dependent manner.

    Evidence T cell activation assays with defined LAM variants and endosomal acidification inhibitors in human cell lines

    PMID:7542404

    Open questions at the time
    • Structural basis for lipid binding unknown
    • Identity of endosomal loading compartment not established
    • Range of presentable lipid antigens undetermined
  2. 1997 High

    Two key requirements for CD1b function were established: β2-microglobulin association is essential for surface expression, and TCR recognition of CD1b-presented GMM depends on headgroup chemistry rather than lipid tail variation, supporting a model where hydrophobic chains are buried in the groove while polar moieties face the TCR.

    Evidence β2m-deficient cell reconstitution with FACS/Western blot readouts; systematic GMM structural analog testing with T cell assays

    PMID:9209486 PMID:9323206

    Open questions at the time
    • Crystal structure of CD1b groove not yet solved
    • Mechanism of lipid loading into the groove unknown
  3. 1999 High

    The early biosynthetic pathway of CD1b was defined: CD1b assembles with phosphatidylinositol in the ER and requires calnexin/calreticulin chaperones for proper folding, distinguishing it from MHC class I assembly and establishing that lipid occupancy begins before the molecule reaches antigen-loading compartments.

    Evidence Mass spectrometry of CD1b-associated lipids; co-immunoprecipitation of ER chaperones with glucosidase inhibitor and proteasome inhibitor experiments

    PMID:10508179 PMID:14722359

    Open questions at the time
    • Whether ER-loaded PI is exchanged in endosomes not directly shown
    • Role of specific ER chaperones in groove filling vs. folding not separated
  4. 2000 High

    The intracellular trafficking itinerary of CD1b was mapped to lysosomal MIIC compartments, and it was shown that some lipids (glycosphingolipids) can load at the cell surface at neutral pH while long-chain mycobacterial antigens require endosomal delivery, establishing that lipid chain length and headgroup chemistry dictate the antigen presentation pathway.

    Evidence Subcellular fractionation, immunofluorescence, cytoplasmic tail mutants, endocytosis inhibitors, and surface-loading assays with GM1 ganglioside and GMM analogs

    PMID:10899914 PMID:10981968 PMID:11015438

    Open questions at the time
    • Adaptor protein sorting signals not fully defined
    • Mechanism of lipid extraction from membranes in lysosomes unknown
  5. 2002 High

    The trafficking pathway was refined to a sequential AP-2→AP-3 sorting model, and lipid tail length was shown to be the key determinant of whether antigen presentation occurs at the surface (short chains) or requires endosomal transit (long chains), explaining how dendritic cells preferentially present long-chain mycobacterial glycolipids.

    Evidence Pulse-chase experiments, dominant-negative AP-2 mutants, synthetic GMM analogs of varying chain length with endocytosis inhibitors in DCs vs. non-professional APCs

    PMID:11847129 PMID:11938350

    Open questions at the time
    • AP-3 involvement inferred but not directly demonstrated by knockout
    • Molecular mechanism of lipid exchange in late endosomes/lysosomes unresolved
  6. 2002 High

    A functional role for CD1b beyond antimicrobial immunity was established: CD1b-restricted T cells recognizing self-lipids promote dendritic cell maturation, demonstrating that CD1b participates in innate-adaptive immune crosstalk even in the absence of infection.

    Evidence Co-culture of CD1b-restricted T cells with DCs, DC maturation marker analysis, cytokine measurement, blocking antibodies

    PMID:12415264

    Open questions at the time
    • Identity of the self-lipid antigens driving DC maturation not determined
    • In vivo relevance of self-lipid-driven DC maturation not tested
  7. 2004 High

    The lipid loading mechanism in lysosomes was resolved by identifying saposin C as a required cofactor that physically interacts with CD1b and extracts lipid antigens from membranes for groove loading, establishing the first lipid transfer protein in the CD1b presentation pathway.

    Evidence SAP-deficient fibroblast reconstitution, co-immunoprecipitation of SAP-C with CD1b, liposome lipid extraction assays, T cell functional assays

    PMID:14716313

    Open questions at the time
    • Structural basis of SAP-C–CD1b interaction unknown
    • Whether SAP-C is sufficient or additional transfer proteins contribute not resolved
  8. 2008 High

    A pH-sensing mechanism within CD1b was identified: ionic tethers formed by residues D60 and E62 act as molecular switches that regulate groove opening at acidic pH, explaining how CD1b selectively loads lipid antigens in late endosomal/lysosomal compartments during its trafficking cycle.

    Evidence Molecular dynamics, site-directed mutagenesis, lipid binding assays at varying pH, T cell activation assays

    PMID:18538591

    Open questions at the time
    • Crystal structure at acidic pH not obtained
    • How pH tethers coordinate with SAP-C-mediated loading not examined
  9. 2011 High

    Multiple structural and biochemical studies converged to define the CD1b groove architecture: crystal structures revealed that scaffold lipids (deoxyceramides, diacylglycerols) fill unoccupied space, enabling the ~2,200 ų groove to present antigens of diverse chain lengths; antigen binding triggers F' pocket closure and surface remodeling that directly influences TCR recognition; and CD1b tetramers proved that cognate TCR-mediated recognition occurs in tuberculosis patients.

    Evidence X-ray crystallography at 1.9 Å of CD1b-diacylsulfoglycolipid complex, comparative lipidomics across CD1 isoforms, CD1b tetramer staining and sorting of patient T cells

    PMID:21807869 PMID:22006319 PMID:22087000

    Open questions at the time
    • Dynamic mechanism of scaffold lipid displacement during antigen loading not visualized
    • Frequency and function of CD1b-reactive T cells in protective immunity not quantified
  10. 2012 High

    CD1e was identified as a second lipid transfer protein in the CD1b pathway, acting specifically to assist α-mannosidase-dependent processing of complex mycobacterial lipoglycans (PIM6) and to transfer processed lipid antigens to CD1b, adding a lipid-editing step to the presentation mechanism.

    Evidence In vitro lipid transfer assays with liposomes, α-mannosidase digestion assays, CD1b-restricted T cell activation with purified CD1e protein reconstitution

    PMID:22782895

    Open questions at the time
    • Whether CD1e and SAP-C act sequentially or redundantly not established
    • Structural basis of CD1e lipid transfer activity unresolved
  11. 2013 High

    The discovery of germline-encoded mycolyl-reactive (GEM) T cells bearing conserved TRAV1-2/TRAJ9 α-chains established that CD1b-reactive T cells include an innate-like population with limited TCR diversity, analogous to invariant NKT cells restricted by CD1d.

    Evidence CD1b tetramers, high-throughput TCR sequencing across unrelated tuberculosis patients, X-ray crystallography, binding affinity measurements

    PMID:23727893

    Open questions at the time
    • Developmental origin and thymic selection of GEM T cells unknown
    • Whether GEM T cells provide protective immunity in tuberculosis not demonstrated
  12. 2016 High

    The ternary crystal structure of GEM TCR–CD1b–GMM revealed that the conserved α-chain docks centrally above CD1b making extensive contacts with both CD1b helices and the glucose headgroup, with α- and β-chains acting as tweezers to grip the sugar moiety, providing the molecular basis for germline-encoded mycobacterial lipid recognition.

    Evidence X-ray crystallography of the ternary TCR-CD1b-GMM complex, site-directed mutagenesis, tuberculosis patient T cell validation

    PMID:27807341

    Open questions at the time
    • How β-chain diversity modulates affinity and specificity not systematically explored
    • No structures of non-GEM TCR-CD1b complexes available at this time
  13. 2019 High

    The structural basis for CD1b autoreactivity was solved: a TCR–CD1b–phosphatidylcholine crystal structure revealed a lateral escape channel in the TCR that shunts variable headgroups away from the binding interface, while the TCR contacts the conserved phosphate neck region, explaining how a single TCR cross-reactively recognizes diverse self-phospholipids but not sphingolipids.

    Evidence X-ray crystallography of ternary TCR-CD1b-phosphatidylcholine complex, functional T cell assays with diverse phospholipid and sphingolipid panels

    PMID:30610190

    Open questions at the time
    • In vivo functional significance of phospholipid-reactive CD1b-restricted T cells unclear
    • Whether lateral escape channel mechanism generalizes to other CD1b-autoreactive TCRs not tested
  14. 2020 High

    CD1b recognition was extended to γδ T cells: Vδ1+ T cells were shown to recognize CD1b through the Vδ1 chain by both lipid-dependent and lipid-independent mechanisms, with some showing dual reactivity to butyrophilin-like molecules, broadening the known immune receptor repertoire engaging CD1b.

    Evidence CD1b tetramers, TCR chain-swap experiments, lipid-free CD1b blocking, butyrophilin co-recognition assays across multiple donors

    PMID:32868441

    Open questions at the time
    • Structural basis of Vδ1–CD1b interaction unknown
    • Physiological role of γδ T cell recognition of CD1b not established
  15. 2023 High

    Comprehensive lipidome profiling confirmed that CD1b is a unique outlier among CD1 proteins, accommodating its groove-to-ligand size mismatch by uniformly seating two small self-lipids per cleft, and differentially editing the self-lipidome based on lipid length and composition, establishing CD1b as a lipid-editing platform.

    Evidence Mass spectrometry-based lipidomics of CD1b-purified lipids compared across all four human CD1 isoforms, integrated with existing crystal structures

    PMID:37725977

    Open questions at the time
    • How dual-lipid occupancy is regulated during antigen loading in vivo not known
    • Whether self-lipidome editing shapes the CD1b-reactive T cell repertoire not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include how CD1b-restricted T cells contribute to protective immunity against tuberculosis in vivo, the structural basis of CD1b recognition by γδ TCRs, the coordination between SAP-C, CD1e, and pH-dependent groove opening during lipid loading, and the developmental biology and thymic selection of GEM and autoreactive CD1b-restricted T cell populations.
  • No in vivo models of CD1b-dependent protective immunity (CD1b is absent in mice)
  • No structure of γδ TCR–CD1b complex
  • Coordination of multiple lipid-loading cofactors not reconstituted in a single system

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 7 GO:0048018 receptor ligand activity 5
Localization
GO:0005764 lysosome 3 GO:0005886 plasma membrane 3 GO:0005768 endosome 2 GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-168256 Immune System 8 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-9609507 Protein localization 3
Complex memberships
CD1b–β2-microglobulin heterodimer

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 Human CD1b presents the mycobacterial lipoglycan lipoarabinomannan (LAM) to αβ T cell receptor-bearing lymphocytes; presentation required internalization and endosomal acidification, and T cell recognition required mannosides with α(1→2) linkages and a phosphatidylinositol unit. T cell activation assays with defined mycobacterial lipoglycan antigens, endosomal acidification inhibitors, and structural variants of LAM Science High 7542404
1997 CD1b presents mycobacterial glucose monomycolate (GMM) to T cells; presentation was insensitive to variations in lipid tails but highly sensitive to chemical alterations in carbohydrate or polar substituents, supporting a model where CD1b's hydrophobic groove binds acyl chains and positions the hydrophilic headgroup for TCR contact. T cell activation assays with chemically defined GMM structural analogs; systematic variation of lipid tails and carbohydrate moieties Science High 9323206
1999 CD1b assembles with phosphatidylinositol (PI) in the endoplasmic reticulum; this association is evolutionarily conserved and PI likely plays a chaperone-like role in CD1 assembly, preserving groove integrity until antigenic lipids are loaded in the endocytic pathway. Lipidomics/mass spectrometry analysis of natural ligands associated with human CD1b; biochemical characterization of CD1-lipid complexes Proceedings of the National Academy of Sciences High 14722359
2000 Glycosphingolipids (e.g., GM1 ganglioside) bind to CD1b on the cell surface at neutral pH and are recognized without internalization or processing; oligosaccharide groups of five or more sugars are required for TCR recognition; binding to CD1b is reversible and non-antigenic ceramide-containing glycosphingolipids can displace GM1. T cell activation assays, soluble CD1b-GM1 complex stimulation, endocytosis inhibitors, systematic variation of oligosaccharide chain length Immunity High 10981968
2000 TCR-mediated recognition of CD1b-presented GMM is highly specific for the precise glucose moiety structure, stereochemistry of the mycolate lipid, and linkage between carbohydrate and lipid; mycobacteria synthesize antigenic GMM by coupling mycobacterial mycolates to host-derived glucose. TCR α and β chain transfection into TCR-deficient cells reconstituting GMM recognition; antigen specificity testing with natural vs. synthetic GMM variants; in vivo tissue infection model The Journal of experimental medicine High 11015438
2000 CD1b accumulates predominantly in lysosomal MHC class II compartments (MIICs), in contrast to CD1c which accumulates in early/late endosomes; deletion of the cytoplasmic tail tyrosine-based internalization motif of CD1c abolished its intracellular localization; CD1b-mediated antigen presentation is sensitive to endosomal acidification inhibitors whereas CD1c-mediated presentation is not, demonstrating distinct intracellular lipid antigen sampling pathways. Subcellular fractionation, immunofluorescence, cytoplasmic tail deletion mutants, pharmacological inhibitors of endosomal acidification, T cell activation assays The Journal of experimental medicine High 10899914
2002 Lipid tail length controls the CD1b antigen presentation pathway: long-chain (C80) GMM analogs require delivery of CD1b and antigen to late endosomes over hours, while short-chain (C32) analogs are presented rapidly by cell-surface CD1b; dendritic cells preferentially present long-chain glycolipids via endosomal loading. T cell activation assays with synthetic GMM analogs of varying chain length, endocytosis inhibitors, cell fractionation comparing DCs vs. non-professional APCs Nature immunology High 11938350
2002 Nascent CD1b is transported rapidly to the cell surface after leaving the Golgi, then internalized via AP-2-dependent sorting at the plasma membrane, followed by a second sorting event (possibly involving AP-3) leading to accumulation in MIICs; newly synthesized CD1b is important for efficient foreign lipid antigen presentation. Pulse-chase experiments, dominant-negative AP-2 mutants, immunofluorescence co-localization, functional T cell presentation assays The EMBO journal High 11847129
2002 CD1b-restricted T cells can promote dendritic cell maturation through recognition of self-lipid antigens presented by CD1b, even in the absence of foreign antigens; distinct CD1 isoforms trigger different costimulatory mechanisms leading to differential IL-12 p70 production. Co-culture of CD1-restricted T cells with DCs, DC maturation markers, cytokine measurement, blocking antibodies Nature immunology High 12415264
2004 Saposin C (SAP-C) is required for lipid antigen presentation by CD1b: fibroblasts deficient in sphingolipid activator proteins (SAPs) transfected with CD1b failed to activate lipid-specific T cells; reconstitution with SAP-C but not other SAPs restored T cell responses; SAP-C directly interacts with CD1b (co-precipitation) and extracts lipid antigen from membranes (liposome assay), co-localizing with lipid antigen in lysosomal compartments. SAP-deficient fibroblast reconstitution, T cell activation assays, co-immunoprecipitation, liposome lipid extraction assays, immunofluorescence co-localization Nature immunology High 14716313
1997 Beta2-microglobulin (β2m) is essential for cell surface expression and transport of CD1b; co-transfection with β2m is required for CD1b to reach the plasma membrane; CD1b is secreted as a complex with endogenous β2m. Transfection of β2m-deficient FO-1 cells with CD1b alone or with β2m, FACS analysis, Western blot, secretion of soluble CD1b constructs European journal of immunology High 9209486
1999 During early biogenesis, CD1b heavy chains associate with both calnexin and calreticulin chaperones in the ER (distinguishing it from MHC class I which associates only with calnexin); prevention of chaperone interaction by castanospermine led to CD1b degradation involving the proteasome and mannosidases; chaperone association is important for CD1b expression during monocyte-to-DC differentiation. Co-immunoprecipitation in β2m-deficient cells, glucosidase inhibitor (castanospermine) treatment, proteasome inhibitors, differentiation model International immunology High 10508179
2003 TCR interactions with CD1b occur on the membrane-distal aspects over α1 and α2 domain helices; site-directed mutagenesis identified CD1b residues critical for TCR interaction, suggesting TCRs bind in a diagonal orientation over the antigen-binding groove making direct contacts with both α helices and bound antigen. Panel of epitope-specific antibodies, site-directed mutagenesis of CD1b, T cell activation assays with mutant CD1b molecules Journal of immunology High 11035089
2003 Fluorescent lipid probe binding assays demonstrated that group 1 CD1 proteins (CD1b and CD1c) show stronger binding of dialkyl-based lipids (phosphatidylcholine, sphingomyelin, ceramide) compared to CD1d; alanine substitution mutants of CD1b distinguish mutations that interfere with ligand binding from those affecting TCR docking. Fluorescent lipid probe (NBD-labeled) binding to soluble recombinant CD1 proteins, competition studies, alanine scanning mutagenesis The Journal of biological chemistry High 14551186
2008 pH-dependent ionic tethers (residues D60, E62) in the CD1b heavy chain near the A' pocket entrance regulate antigen capture: these tethers link the rigid α1 helix to flexible areas of the α2 helix and 50-60 loop; disruption by acidic pH or mutation increased lipid association/dissociation rates and enabled preferential presentation of antigens with bulky lipid tails, acting as molecular switches during endosomal recycling. Molecular dynamics modeling, site-directed mutagenesis, lipid binding assays at varying pH, T cell activation assays with mutant CD1b Immunity High 18538591
2011 Crystal structure of CD1b bound to a mycobacterial diacylsulfoglycolipid reveals that upon antigen binding, endogenous spacer lipids (diradylglycerols) are displaced within the binding groove, accompanied by F' pocket closure and extensive rearrangement of residues at the TCR-recognition surface, reducing A' pocket capacity and causing incomplete embedding of hydrophobic antigen motifs — explaining why aliphatic tail modifications affect T cell recognition. X-ray crystallography (1.9 Å resolution), site-directed mutagenesis, T cell stimulation assays Proceedings of the National Academy of Sciences High 22006319
2011 CD1b-specific scaffold lipids were identified as deoxyceramides and diacylglycerols using comparative lipidomics; these scaffold lipids lack a hydrophilic head group and seat below the antigen within the large CD1b groove (volume ~2,200 ų), allowing CD1b to simultaneously bind one small scaffold and one small antigenic lipid, thereby extending the range of presentable antigen chain lengths. Comparative lipidomics (mass spectrometry), crystal structure analysis, T cell activation assays demonstrating scaffold function in augmenting antigen presentation Proceedings of the National Academy of Sciences High 22087000
2011 CD1b tetramers loaded with GMM directly bind αβ TCRs from tuberculosis patients; CD1b-glycolipid complexes stain a small subpopulation of CD4+ T cells in blood from M. tuberculosis-infected humans; polyclonal T cells sorted with tetramers are activated by GMM presented by CD1b, proving a cognate TCR-mediated recognition mechanism. Fluorescent CD1b tetramer staining, TCR blocking with recombinant clonotypic TCR, ex vivo T cell sorting and functional activation assays The Journal of experimental medicine High 21807869
2013 A conserved population of human T cells (GEM T cells) bearing TRAV1-2/TRAJ9 α-chains with few N-region additions recognizes CD1b presenting mycobacterial mycolyl lipids; high-throughput TCR sequencing, tetramer binding, and crystallography linked α-chain sequence motifs to high-affinity CD1b recognition. CD1b tetramers, high-throughput TCR sequencing, X-ray crystallography, binding affinity measurements, T cell functional assays from tuberculosis patients Nature immunology High 23727893
2016 Crystal structure of a GEM TCR bound to CD1b presenting glucose-6-O-monomycolate (GMM) shows the TCR docks centrally above CD1b with the conserved TCR α-chain making extensive contacts with both CD1b and GMM; both TCR α- and β-chains act as tweezers to grip the glucose moiety, providing a highly specific recognition mechanism for this mycobacterial glycolipid. X-ray crystallography of TCR-CD1b-GMM ternary complex, site-directed mutagenesis, T cell functional assays from tuberculosis patients Nature communications High 27807341
2012 CD1e behaves as a lipid transfer protein required for CD1b-mediated presentation of mycobacterial PIM6: CD1e assists α-mannosidase-dependent digestion of PIM6 selectively based on degree of acylation, and directly transfers diacylated PIM from donor membranes to acceptor liposomes and to CD1b. Lipid transfer assays with liposomes, α-mannosidase digestion assays, CD1b-restricted T cell activation assays, reconstitution with purified CD1e protein The Journal of biological chemistry High 22782895
2015 CD1b autoreactive T cells in humans recognize CD1b-phospholipid complexes through αβ TCRs; phosphatidylglycerol (PG) was identified as the immunodominant self-lipid antigen; T cells do not discriminate between mammalian and bacterial PG, suggesting recognition of infection- or stress-associated lipids. CD1b dextramers for T cell isolation, mass spectrometry for lipid identification, T cell activation assays scanning major phospholipid classes, TCR-blocking experiments Proceedings of the National Academy of Sciences High 26621732
2019 Crystal structure of a TCR bound to CD1b-phosphatidylcholine reveals a lateral escape channel in the TCR that shunts phospholipid head groups sideways along the CD1b-TCR interface without TCR contact; TCR recognition targets the neck-region phosphate common to all major self-phospholipids but absent in sphingolipids, providing a molecular mechanism for promiscuous cross-reactive recognition of diverse phospholipids. X-ray crystallography of TCR-CD1b-phosphatidylcholine ternary complex, T cell activation assays with diverse phospholipids and sphingolipids Nature communications High 30610190
2003 During dendritic cell maturation induced by LPS, CD1b undergoes constitutive clathrin-mediated endocytosis and accumulates in reorganized lysosomal compartments (mature dendritic cell lysosomes), unlike MHC class II which redistributes to the plasma membrane; the steady-state distribution of CD1b remains intracellular/lysosomal despite maturation. Electron microscopy, immunofluorescence, transferrin receptor endocytosis assay as control, subcellular fractionation in monocyte-derived DCs Molecular biology of the cell High 12925770
2005 M. tuberculosis upregulates group 1 CD1 proteins (including CD1b) on myeloid precursors via TLR-2 signaling through mycobacterial polar lipids; this upregulation occurs via transcriptional regulation and new CD1 protein synthesis; TLR-2 is necessary for CD1b protein expression upregulation, while CD1d is concomitantly downregulated. Normal phase chromatography fractionation of M. tuberculosis products, purified natural and synthetic TLR ligands, TLR-2 knockout cells, RT-PCR and flow cytometry for CD1 expression Journal of immunology High 16034117
1998 Mouse CD1 (mCD1) localizes to endosomes and co-localizes extensively with DM molecules; the tyrosine in the cytoplasmic tail sequence is required for endosomal localization (shown by site-directed mutagenesis); at least some CD1-autoreactive T cells require endosomally-derived CD1-bound self-ligands. Site-directed mutagenesis of cytoplasmic tail tyrosine, immunofluorescence co-localization with DM, T cell hybridoma reactivity to wild-type vs. mutant CD1 Journal of immunology High 9558068
2020 Human γδ T cells expressing Vδ1 recognize CD1b by at least two distinct mechanisms: some require carried lipid antigens, others do not; CD1b specificity is mediated by the Vδ1 chain (demonstrated by chain-swap experiments); one CD1b-specific Vδ1+/Vγ4+ TCR shows dual reactivity to CD1b and butyrophilin-like proteins. CD1b tetramers for donor-unrestricted T cell identification, TCR chain-swap experiments, blocking with lipid-free CD1b, co-recognition assays with butyrophilin-like proteins Proceedings of the National Academy of Sciences High 32868441
2008 HCMV inhibits CD1 antigen presentation by two mechanisms: (1) transcriptional inhibition by the viral cmvIL-10 homologue, and (2) post-transcriptional blockade of CD1 localization to the cell surface; the post-transcriptional block is distinct from known HCMV MHC class I-blocking molecules. HCMV infection of DCs, flow cytometry for CD1 surface expression, RT-PCR for transcription, comparison of cmvIL-10 deletion mutants Journal of virology Medium 18287231
2000 CD1a, CD1b, and CD1c expression partially inhibits NK cell-mediated target cell lysis; this inhibitory effect was demonstrated by expression of individual CD1 proteins in transfected NK-sensitive targets, was reversible by anti-CD1 monoclonal antibodies, and was augmented by bacterial glycolipid antigens bound to CD1. CD1 transfection into NK-sensitive targets, NK cell killing assays, antibody blocking, effect of lipid antigen loading Journal of immunology Medium 10843662
2023 CD1b lipidome analysis reveals >2,000 CD1-lipid complexes; CD1b is the outlier among CD1 proteins showing extreme size mismatch between its large groove (~2,200 ų) and small self-lipid ligands, resolved by uniformly seating two small lipids in one cleft; CD1b differentially edits the self-lipidome based on lipid length and chemical composition. Lipidomics/mass spectrometry of CD1b-purified lipids, comparison across four CD1 isoforms, integration with existing crystal structures Cell High 37725977
2011 Borrelia burgdorferi induces upregulation of CD1b and CD1c on dendritic cells through TLR-2 activation followed by release of soluble factors; IL-1β was identified as a previously unknown signaling intermediate in this pathway, acting in trans to upregulate group 1 CD1 proteins on DC precursors. B. burgdorferi infection of monocyte-derived DCs, conditioned medium transfer experiments, cytokine neutralization (anti-IL-1β), TLR-2 stimulation, flow cytometry for CD1 expression, analysis of Lyme disease patient skin biopsies European journal of immunology Medium 21246541

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Mouse CD1-specific NK1 T cells: development, specificity, and function. Annual review of immunology 986 9143699
2004 CD1: antigen presentation and T cell function. Annual review of immunology 800 15032598
1995 CD1-restricted T cell recognition of microbial lipoglycan antigens. Science (New York, N.Y.) 606 7542404
1999 The CD1 system: antigen-presenting molecules for T cell recognition of lipids and glycolipids. Annual review of immunology 507 10358761
1997 Structural requirements for glycolipid antigen recognition by CD1b-restricted T cells. Science (New York, N.Y.) 352 9323206
1989 Two classes of CD1 genes. European journal of immunology 230 2467814
2009 Antigen Presentation by CD1 Lipids, T Cells, and NKT Cells in Microbial Immunity. Advances in immunology 200 19477319
2005 Human CD1-restricted T cell recognition of lipids from pollens. The Journal of experimental medicine 190 16009719
2002 Presentation of the same glycolipid by different CD1 molecules. The Journal of experimental medicine 179 11956292
2013 A conserved human T cell population targets mycobacterial antigens presented by CD1b. Nature immunology 171 23727893
1998 CD1.1 expression by mouse antigen-presenting cells and marginal zone B cells. Journal of immunology (Baltimore, Md. : 1950) 171 9531266
2002 CD1-dependent dendritic cell instruction. Nature immunology 163 12415264
2002 CD1-mediated gamma/delta T cell maturation of dendritic cells. The Journal of experimental medicine 158 12486100
2003 Intracellular pathways of CD1 antigen presentation. Nature reviews. Immunology 150 12511872
1999 Diverse TCRs recognize murine CD1. Journal of immunology (Baltimore, Md. : 1950) 149 9886382
2016 The Immunology of CD1- and MR1-Restricted T Cells. Annual review of immunology 138 26927205
2005 Anatomy of CD1-lipid antigen complexes. Nature reviews. Immunology 136 15864273
1988 Mouse CD1 is distinct from and co-exists with TL in the same thymus. The EMBO journal 136 2460336
2004 Saposin C is required for lipid presentation by human CD1b. Nature immunology 134 14716313
2000 The alphabeta T cell response to self-glycolipids shows a novel mechanism of CD1b loading and a requirement for complex oligosaccharides. Immunity 130 10981968
2002 Lipid length controls antigen entry into endosomal and nonendosomal pathways for CD1b presentation. Nature immunology 124 11938350
1998 Tissue-specific recognition of mouse CD1 molecules. Journal of immunology (Baltimore, Md. : 1950) 123 9531267
2015 Lipid and small-molecule display by CD1 and MR1. Nature reviews. Immunology 120 26388332
1998 Mouse CD1-autoreactive T cells have diverse patterns of reactivity to CD1+ targets. Journal of immunology (Baltimore, Md. : 1950) 117 9558068
2000 CD1b-mediated T cell recognition of a glycolipid antigen generated from mycobacterial lipid and host carbohydrate during infection. The Journal of experimental medicine 111 11015438
2011 CD1b tetramers bind αβ T cell receptors to identify a mycobacterial glycolipid-reactive T cell repertoire in humans. The Journal of experimental medicine 107 21807869
1999 CD1 expression in human atherosclerosis. A potential mechanism for T cell activation by foam cells. The American journal of pathology 101 10487835
2005 Mycobacterium tuberculosis regulates CD1 antigen presentation pathways through TLR-2. Journal of immunology (Baltimore, Md. : 1950) 93 16034117
1995 In human dermis, ultraviolet radiation induces expansion of a CD36+ CD11b+ CD1- macrophage subset by infiltration and proliferation; CD1+ Langerhans-like dendritic antigen-presenting cells are concomitantly depleted. The Journal of investigative dermatology 89 7490472
2000 CD1-restricted T-cell responses and microbial infection. Nature 87 10963609
1991 Isolation and expression of cDNA encoding the murine homologues of CD1. Journal of immunology (Baltimore, Md. : 1950) 81 1702817
2002 Intracellular trafficking pathway of newly synthesized CD1b molecules. The EMBO journal 76 11847129
2000 Human CD1b and CD1c isoforms survey different intracellular compartments for the presentation of microbial lipid antigens. The Journal of experimental medicine 76 10899914
2007 CD1-restricted recognition of exogenous and self-lipid antigens by duodenal gammadelta+ T lymphocytes. Journal of immunology (Baltimore, Md. : 1950) 69 17339459
2009 Preterm and term cervical ripening in CD1 Mice (Mus musculus): similar or divergent molecular mechanisms? Biology of reproduction 67 19684330
2004 Lipid-protein interactions: biosynthetic assembly of CD1 with lipids in the endoplasmic reticulum is evolutionarily conserved. Proceedings of the National Academy of Sciences of the United States of America 66 14722359
1988 CD1c but neither CD1a nor CD1b molecules are expressed on normal, activated, and malignant human B cells: identification of a new B-cell subset. Blood 66 3260523
2014 γδ T cell surveillance via CD1 molecules. Trends in immunology 64 25283967
2015 Human autoreactive T cells recognize CD1b and phospholipids. Proceedings of the National Academy of Sciences of the United States of America 63 26621732
1999 The molecular basis of CD1-mediated presentation of lipid antigens. Immunological reviews 62 10631954
2011 Discovery of deoxyceramides and diacylglycerols as CD1b scaffold lipids among diverse groove-blocking lipids of the human CD1 system. Proceedings of the National Academy of Sciences of the United States of America 61 22087000
2016 T cell receptor recognition of CD1b presenting a mycobacterial glycolipid. Nature communications 60 27807341
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