| 1992 |
CD1b functions as an antigen-presenting molecule that restricts the proliferative and cytotoxic responses of CD4-CD8- αβ TCR+ T cells specific for Mycobacterium tuberculosis, requiring CD1b expression on the antigen-presenting cell and involving an antigen processing requirement similar to MHC class II-restricted presentation. |
T cell proliferation and cytotoxicity assays with CD1b-expressing antigen-presenting cells; antibody blocking experiments |
Nature |
High |
1281285
|
| 1996 |
CD1b localizes to MHC class II compartments (MIICs) — the endosomal antigen-loading compartments — and this localization is dependent on a tyrosine-based motif in its own cytoplasmic tail, not on association with invariant chain as for MHC class II. |
Immunoelectron microscopy, subcellular fractionation, cytoplasmic tail deletion/mutation constructs, and co-localization with MHC class II in MIICs |
Science |
High |
8662520
|
| 1997 |
CD1b presents the mycobacterial glycolipid glucose monomycolate (GMM) to T cells; T cell recognition is insensitive to variation in lipid tails but extremely sensitive to alterations in the carbohydrate or polar head group, indicating that CD1b binds acyl chains nonspecifically in its hydrophobic groove while positioning the hydrophilic moiety for specific TCR interaction. |
Synthetic GMM analogs with defined chemical modifications presented to CD1b-restricted T cell clones; T cell activation assays |
Science |
High |
9323206
|
| 1997 |
The macrophage mannose receptor (MR) mediates uptake of lipoarabinomannan (LAM) and delivers it to late endosomes/lysosomes/MIICs where CD1b is present; MR and CD1b colocalize in these compartments, linking innate pattern recognition to CD1b-mediated adaptive T cell presentation of LAM. |
MR antagonism/blocking assays, LAM internalization studies, immunofluorescence colocalization of MR, LAM, and CD1b in intracellular compartments |
Immunity |
High |
9047240
|
| 1998 |
CD1b directly binds the acyl side chains of lipid antigens (LAM, phosphatidylinositol mannoside, GMM) with high affinity; binding is optimal at acidic pH due to partial unfolding of the α-helices of CD1b at low pH, revealing a hydrophobic binding site. |
Direct CD1b-antigen binding assays, pH-dependent binding experiments, structural/biochemical characterization |
Immunity |
High |
9529150
|
| 1998 |
The nine-amino acid cytoplasmic tail of CD1b, specifically the single cytoplasmic tyrosine residue, is required for endosomal targeting of CD1b and for efficient presentation of lipid antigens; CD1b mutants lacking this motif are expressed on the cell surface but fail to efficiently present antigens acquired exogenously or from live intracellular organisms. |
Site-directed mutagenesis of cytoplasmic tail tyrosine, functional antigen presentation assays with T cell lines, subcellular localization studies |
Immunity |
High |
9529151
|
| 1999 |
Nascent CD1b heavy chains interact with the ER chaperones calnexin and calreticulin prior to β2-microglobulin binding; prevention of these chaperone interactions leads to proteasome- and mannosidase-dependent degradation of CD1b; β2-microglobulin rescues chaperone-unassociated CD1b from degradation. |
Co-immunoprecipitation of CD1b with calnexin/calreticulin, glucosidase inhibitor (castanospermine) treatment, proteasome inhibitor experiments, β2-microglobulin rescue assays in β2m-deficient cells |
International immunology |
High |
10508179
|
| 2000 |
Self-glycosphingolipids (e.g., GM1 ganglioside) bind to CD1b on the cell surface at neutral pH and are recognized without internalization or processing; binding is highly reversible and other ceramide-containing glycosphingolipids can displace GM1, acting as competitive blockers. This contrasts with the endosomal loading pathway used for exogenous mycobacterial lipids. |
Cell surface CD1b-lipid binding assays at neutral pH, soluble GM1-CD1b complex T cell stimulation, competitive displacement assays, inhibitor studies |
Immunity |
High |
10981968
|
| 2000 |
TCR interactions with CD1b occur on the membrane-distal aspects over the α1 and α2 domain helices; TCRs bind in a diagonal orientation relative to the longitudinal axes of the α-helices, making contacts with both helices and bound antigen simultaneously, similar to but distinct from TCR-MHC interactions. |
Epitope-specific antibody panel mapping and site-specific CD1b mutants tested for T cell recognition |
Journal of Immunology |
Medium |
11035089
|
| 2002 |
Newly synthesized CD1b is transported rapidly to the cell surface from the Golgi and then enters the endocytic system via AP-2-dependent internalization at the plasma membrane, followed by a second sorting event (possibly involving AP-3) that delivers it to MIICs; this trafficking pathway via the cell surface is important for efficient lipid antigen presentation. |
Pulse-chase experiments, AP-2 dominant-negative inhibition, inhibitor studies, functional antigen presentation assays |
The EMBO Journal |
High |
11847129
|
| 2002 |
Lipid chain length determines whether CD1b-mediated antigen presentation occurs via endosomal or cell-surface pathways: long-chain (C80) GMM antigens require delivery of CD1b and antigen to late endosomes over several hours, while short-chain (C32) analogs are presented rapidly by cell-surface CD1b. Dendritic cells preferentially present long-chain glycolipids due to efficient endosomal delivery. |
Synthetic GMM analogs of defined chain lengths, endosomal inhibitors, comparison of professional vs. nonprofessional APCs, intracellular trafficking studies |
Nature Immunology |
High |
11938350
|
| 2004 |
Saposin C (SAP-C) is required for CD1b-mediated lipid antigen presentation: SAP-C-deficient fibroblasts expressing CD1b fail to activate lipid-specific T cells, and this is rescued by reconstitution with SAP-C but not other SAPs. SAP-C directly interacts with CD1b (demonstrated by co-precipitation), colocalizes with lipid antigen in lysosomal compartments, and efficiently extracts lipid antigen from membranes. |
SAP-deficient fibroblast reconstitution, co-immunoprecipitation of SAP-C with CD1b, liposome lipid extraction assays, immunofluorescence colocalization |
Nature Immunology |
High |
14716313
|
| 2008 |
pH-dependent ionic tethers in the CD1b heavy chain (residues D60, E62) connect the rigid α1 helix to flexible regions of the α2 helix and the 50-60 loop; disruption of these tethers by acidic pH or mutation increases lipid association and dissociation with CD1b and preferentially promotes presentation of antigens with bulky lipid tails, functioning as molecular switches that respond to pH during endosomal recycling. |
Molecular dynamics modeling, mutagenesis of D60/E62, lipid binding assays at varying pH, functional antigen presentation assays |
Immunity |
High |
18538591
|
| 2011 |
CD1b uses endogenous scaffold lipids (specifically deoxyceramides and diacylglycerols identified by lipidomics) seated below the antigen in its large groove; these scaffolds lack hydrophilic head groups and function to augment presentation of small glycolipid antigens, enabling CD1b to present antigens with an unusually broad range of chain lengths. |
Comparative lipidomics of CD1 proteins, crystal structure analysis of CD1b with scaffold lipids, functional antigen presentation assays with scaffold lipids |
PNAS |
High |
22087000
|
| 2011 |
A crystal structure of CD1b bound to mycobacterial diacylsulfoglycolipid (at 1.9 Å) reveals that antigen binding causes repositioning of endogenous spacer lipids (diradylglycerols) within the groove, F' pocket closure, and extensive rearrangement of residues exposed to TCRs, including reduction of A' pocket capacity and incomplete embedding of the methyl-ramified phthioceranoyl chain — explaining why hydrophobic tail modifications are critical for T cell recognition. |
1.9 Å crystal structure of CD1b-diacylsulfoglycolipid complex, site-directed mutagenesis, functional T cell stimulation assays |
PNAS |
High |
22006319
|
| 2012 |
CD1e functions as a lipid transfer protein that assists α-mannosidase-dependent processing of hexamannosylated phosphatidylinositol mannosides (PIM6) for CD1b presentation; CD1e selectively assists digestion of PIM6 species according to acylation degree and transfers only diacylated PIM from membranes to CD1b. |
Lipid transfer assays from donor to acceptor liposomes, membrane-to-CD1b transfer assays, enzymatic digestion assays with defined PIM substrates |
Journal of Biological Chemistry |
High |
22782895
|
| 2016 |
Crystal structure of a GEM TCR bound to CD1b presenting glucose-6-O-monomycolate (GMM) shows the GEM TCR docks centrally above CD1b with the conserved TCR α-chain extensively contacting both CD1b and the glucose moiety of GMM; both TCR α- and β-chains act as 'tweezers' to grip the glucose head group, creating highly specific mycobacterial glycolipid recognition. |
Crystal structure of GEM TCR-CD1b-GMM ternary complex, mutagenesis of TCR contact residues, functional T cell assays with tuberculosis patient cells |
Nature Communications |
High |
27807341
|
| 2019 |
CD1b-autoreactive T cells recognize common self-phospholipids (phosphatidylcholine, phosphatidylinositol, phosphatidylethanolamine) via a 'lateral escape channel' in the TCR that shunts phospholipid head groups sideways along the CD1b-TCR interface without contacting the TCR; the TCR recognition site contacts the phosphate neck region common to all major self-phospholipids but absent in sphingolipids, explaining broad cross-reactivity. |
Crystal structure of TCR-CD1b-phosphatidylcholine complex, T cell activation assays with diverse phospholipids |
Nature Communications |
High |
30610190
|
| 2020 |
Human γδ T cells with Vδ1-containing TCRs recognize CD1b by at least two distinct mechanisms: some require lipid antigen, others do not; CD1b specificity is mediated by the Vδ1 chain (demonstrated by chain swap experiments); one Vδ1+Vγ4+ TCR shows dual reactivity to CD1b and butyrophilin-like proteins. |
CD1b tetramers, TCR chain swap experiments, CD1b blocking assays, multiple donor analysis |
PNAS |
Medium |
32868441
|
| 2022 |
Crystal structure (1.9 Å) of CD1b presenting self-phosphatidylinositol-C34:1 with an endogenous scaffold lipid, and (2.4 Å) of this complex bound to the autoreactive BC8B αβ TCR; TCR contacts both the phosphoinositol headgroup and glycerol neck via antigen remodeling within CD1b; alanine scanning mutagenesis identified Glu-80 of CD1b as critical for TCR binding; both CD1b α1 and α2 domains modulate the interaction. |
1.9 Å and 2.4 Å crystal structures, alanine scanning mutagenesis, surface plasmon resonance |
Journal of Biological Chemistry |
High |
36587766
|
| 2000 |
CD1b-restricted T cell recognition of GMM requires a precise stereospecific epitope: the exact glucose structure, stereochemistry of the mycolate lipid, and the linkage between carbohydrate and lipid are all required; mycobacteria generate antigenic GMM by coupling mycobacterial mycolates to host-derived glucose, creating an epitope formed by interaction of host and pathogen biosynthetic pathways. |
TCR α/β chain transfection reconstitution of GMM recognition, chemical characterization of GMM produced in infected tissue, mycobacterial mutant and in vivo infection studies |
Journal of Experimental Medicine |
High |
11015438
|
| 2000 |
CD1b and CD1c traffic to different intracellular compartments: CD1b accumulates predominantly in lysosomal MHC class II compartments (MIICs), while CD1c accumulates in early/late endosomes. CD1b-mediated antigen presentation requires endosomal acidification and endosomal localization of CD1b, while CD1c-mediated presentation does not require these. |
Subcellular fractionation, immunofluorescence in dendritic cells, endosomal acidification inhibitors, cytoplasmic tail deletion mutants, functional antigen presentation assays |
Journal of Experimental Medicine |
High |
10899914
|
| 2000 |
GPI-anchored CD1b (CD1b.DAF) is less efficient than native CD1b in antigen presentation, demonstrating that the CD1b cytoplasmic tail-dependent endosomal trafficking pathway is required for optimal antigen loading, distinct from CD1c which maintains presentation capacity when GPI-reanchored. |
GPI-reanchored CD1b chimeric constructs, phospholipase C sensitivity assay confirming GPI modification, T cell cytotoxicity and cytokine release functional assays |
Journal of Immunology |
Medium |
10903726
|
| 2011 |
CD1b-GMM fluorescent tetramers bind αβ TCRs directly (blocked by recombinant clonotypic TCR comprised of TRAV17 and TRBV4-1), proving a cognate mechanism of CD1b-glycolipid complex recognition by the TCR; nearly all CD1b tetramer-detected cells express CD4 co-receptor, contrary to prior emphasis on CD8+ and DN clones. |
Fluorescent CD1b tetramer staining, recombinant TCR blocking, polyclonal T cell sorting and functional activation, ex vivo analysis from TB-infected donors |
Journal of Experimental Medicine |
High |
21807869
|
| 2015 |
CD1b-autoreactive T cells recognize CD1b-phospholipid complexes via αβ TCRs; phosphatidylglycerol (PG) is the immunodominant self-lipid antigen; T cells do not discriminate mammalian from bacterial PG, suggesting recognition of infection- or stress-associated lipids. Identified using CD1b dextramers. |
CD1b polyvalent dextramer staining, mass spectrometry identification of lipid antigens, T cell activation assays scanning major phospholipid classes |
PNAS |
High |
26621732
|