Molecular Interaction of CD1b with Lipoglycan Antigens

Ernst, William; Maher, Juli K.; Cho, Sungae; Niazi, Kayvan; Chatterjee, Delphi; Moody, D. Branch; Besra, Gurdyal S.; Watanabe, Yutaka; Jensen, Peter E.; Porcelli, Steven A.; Kronenberg, Mitchell; Modlin, Robert L.

doi:10.1016/s1074-7613(00)80538-5

Cited by 175 publications

(150 citation statements)

References 37 publications

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“…Similar to processing/presentation of MHC class II-restricted protein Ags, chloroquine inhibits CD1b-mediated T cell stimulation (5,28,29). Moreover, the CD1b molecule accommodates its ligands more efficiently when loading is performed at low pH, which probably facilitates widening of the groove (30). It can also be speculated that glycolipids are processed by host cell-derived lysosomal enzymes, which have lower pH optima.…”

Section: Discussionmentioning

confidence: 99%

Intersection of Group I CD1 Molecules and Mycobacteria in Different Intracellular Compartments of Dendritic Cells

Schaible

Hagens

Fischer

et al. 2000

The Journal of Immunology

109

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Human CD1a, CD1b, and CD1c molecules can present mycobacterial glycolipids to T cells. Because phagosomes containing viable mycobacteria represent early endosomal compartments, we studied where mycobacterial glycolipids intersect with CD1 molecules in infected APC. CD1b and CD1c, but not CD1a, localized to late endosomes/lysosomes. CD1a and CD1c were predominantly expressed on the cell surface and in mycobacterial phagosomes of the early endosomal stage. In contrast, CD1b was present in a subset of mycobacterial phagosomes representing mature phagolysosomes. Released mycobacterial glycolipids including lipoarabinomannan and phosphatidylinositol mannosides were transported from the phagosome into late endosomes/lysosomes and to uninfected bystander cells. The macrophage mannose receptor, which has been implicated in glycolipid uptake by APC for CD1b-mediated presentation, was absent from mycobacterial phagosomes and may therefore not be involved in trafficking of glycolipids between phagosomes and late endosomes/lysosomes. In conclusion, all three CD1 molecules have access to mycobacteria and glycolipids thereof, but at different intracellular sites. This allows sampling by CD1a, CD1b, and CD1c of mycobacterial glycolipids from different intracellular sites of the infected cell, which has important implications for processing and presentation of such Ags during mycobacterial infections.

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Section: Discussionmentioning

confidence: 99%

Intersection of Group I CD1 Molecules and Mycobacteria in Different Intracellular Compartments of Dendritic Cells

Schaible

Hagens

Fischer

et al. 2000

The Journal of Immunology

109

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“…Indeed, we found that the structurally different parietal and cellular ManLAM PI anchors differentially stimulate interleukin-8 and tumour necrosis factor-α secretion from human dendritic cells [11]. Moreover it is likely that PI anchor plays a crucial role in ManLAM presentation to αβT cells by CD1 molecules [41]. CD1 glycoproteins are characterized by a hydrophobic groove which corresponds to the antigen-binding site [20].…”

Section: Discussionmentioning

confidence: 87%

“…CD1 glycoproteins are characterized by a hydrophobic groove which corresponds to the antigen-binding site [20]. It is quite clear that ManLAM binding to CD1 occurs through the hydrophobic interactions between ManLAM fatty acids and non-polar amino acids of the CD1 groove [41]. So, subtle differences in the PI anchor concerning the degree of acylation (from 1 to 4 fatty acids), the acylation site (glycerol, Manp, myo-inositol) and the nature of the fatty acids [palmitic, tuberculostearic, stearic, 12-O-(methoxypropanoyl)-12-hydroxystearic acids], probably discriminate ManLAM CD1 binding.…”

Section: Discussionmentioning

confidence: 99%

Lipoarabinomannans: characterization of the multiacylated forms of the phosphatidyl-myo-inositol anchor by NMR spectroscopy

Nigou

Gilleron

Puzo

1999

Biochemical Journal

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Lipoarabinomannans, which exhibit a large spectrum of immunological activities, emerge as the major antigens of mycobacterial envelopes. The lipoarabinomannan structure is based on a phosphatidyl-myo-inositol anchor whose integrity has been shown to be crucial for lipoarabinomannan biological activity and particularly for presentation to CD4/CD8 double-negative αβT cells by CD1 molecules. In this report, an analytical approach was developed for high-resolution 31P-NMR analysis of native, i.e. multiacylated, lipoarabinomannans. The one-dimensional 31P spectrum of cellular lipoarabinomannans, from Mycobacterium bovis Bacillus Calmette–Guérin, exhibited four 31P resonances typifying four types of lipoarabinomannans. Two-dimensional 1H-31P heteronuclear multiple-quantum-correlation/homonuclear Hartmann–Hahn analysis of the native molecules showed that these four types of lipoarabinomannan differed in the number and localization of fatty acids (from 1 to 4) esterifying the anchor. Besides the three acylation sites previously described, i.e. positions 1 and 2 of glycerol and 6 of the mannosyl unit linked to the C-2 of myo-inositol, we demonstrate the existence of a fourth acylation position at the C-3 of myo-inositol. We report here the first structural study of native multiacylated lipoarabinomannans, establishing the structure of the intact phosphatidyl-myo-inositol anchor. Our findings would help gain more understanding of the molecular basis of lipoarabinomannan discrimination in the binding process to CD1 molecules.

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“…In fact, both CD1b and MHC class II molecules may load Ags in the same types of late endosomal compartments (13). Late endosomes are thought to possess a milieu amenable to the loading of CD1b with Ags, given their acidic pH and the presence of CD1b-binding Ags (11,13,14,30). Significantly, only a minority of GPI-anchored molecules, which lack a cytoplasmic tyrosine-based targeting motif, transit into this late endosomal compartment that is thought to be essential for CD1b Ag loading.…”

Section: Discussionmentioning

confidence: 99%

Glycosyl-Phosphatidylinositol Reanchoring Unmasks Distinct Antigen-Presenting Pathways for CD1b and CD1c

Geho

Fayen

Jackman

et al. 2000

The Journal of Immunology

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Human CD1 proteins present lipid and glycolipid Ags to T cells. Cellular trafficking patterns of CD1 proteins may determine the ability of differing isoforms of CD1 to acquire, bind, and present these Ags to T cells. To test this hypothesis, glycosyl-phosphatidylinositol (GPI)-modified variants of CD1b and CD1c were engineered by chimerization with a GPI modification signal sequence derived from decay-accelerating factor (DAF). GPI reanchoring was confirmed by demonstrating the phosphatidylinositol-specific phospholipase C sensitivity of the CD1b · DAF and CD1c · DAF fusion proteins expressed on transfectant cell surfaces. Using cytotoxicity and cytokine release assays as functional readouts, we demonstrated that CD1c · DAF is as efficient as native CD1c in presenting mycobacterial Ags to the human CD1c-restricted T cell line CD8-1. In contrast, CD1b · DAF, although also capable of presenting Ag (in this case to the CD1b-restricted T cell line LDN5), was less efficient than its native CD1b counterpart. The data support the idea that CD1c · DAF maintains the capacity to access CD1c Ag-loading compartment(s), whereas CD1b · DAF is diverted by its GPI anchor away from the optimal CD1b Ag-loading compartment(s). This constitutes the first GPI reanchoring of CD1 proteins and provides evidence that CD1b and CD1c have nonoverlapping Ag-presenting pathways, suggesting that these two Ag-presenting molecules may have distinct roles in lipid Ag presentation.

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Molecular Interaction of CD1b with Lipoglycan Antigens

Cited by 175 publications

References 37 publications

Intersection of Group I CD1 Molecules and Mycobacteria in Different Intracellular Compartments of Dendritic Cells

Intersection of Group I CD1 Molecules and Mycobacteria in Different Intracellular Compartments of Dendritic Cells

Lipoarabinomannans: characterization of the multiacylated forms of the phosphatidyl-myo-inositol anchor by NMR spectroscopy

Glycosyl-Phosphatidylinositol Reanchoring Unmasks Distinct Antigen-Presenting Pathways for CD1b and CD1c

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