Two classes of CD1 genes

Calabi, Franco; Jarvis, John M.; Martin, Luis; Milstein, C.

doi:10.1002/eji.1830190211

Cited by 249 publications

(167 citation statements)

References 21 publications

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“…Five different isotypes of CD1 proteins are expressed in association with ␤ 2 -microglobulin (␤ 2 m) 3 and can be categorized into two groups: group I (CD1a, CD1b, CD1c and CD1e (being intermediate) in humans) and group II (CD1d in humans and mice) based on sequence homology (2). Unlike MHC molecules that present peptides, CD1 proteins bind and display a wide array of lipids, glycolipids, and lipopeptides (either foreign or self) to T lymphocytes expressing ␣-and ␤-chains of the TCR (3).…”

Section: Involvement Of Secretory and Endosomal Compartments Inmentioning

confidence: 99%

Involvement of Secretory and Endosomal Compartments in Presentation of an Exogenous Self-Glycolipid to Type II NKT Cells

Roy

Maricic

Khurana

et al. 2008

The Journal of Immunology

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Natural Killer T (NKT) cells recognize both self and foreign lipid Ags presented by CD1 molecules. Although presentation of the marine sponge-derived lipid αGalCer to type I NKT cells has been well studied, little is known about self-glycolipid presentation to either type I or type II NKT cells. Here we have investigated presentation of the self-glycolipid sulfatide to a type II NKT cell that specifically recognizes a single species of sulfatide, namely lyso-sulfatide but not other sulfatides containing additional acyl chains. In comparison to other sulfatides or αGalCer, lyso-sulfatide binds with lower affinity to CD1d. Although plate-bound CD1d is inefficient in presenting lyso-sulfatide at neutral pH, it is efficiently presented at acidic pH and in the presence of saposin C. The lysosomal trafficking of mCD1d is required for αGalCer presentation to type I NKT cells, it is not important for presentation of lyso-sulfatide to type II NKT cells. Consistently, APCs deficient in a lysosomal lipid-transfer protein effectively present lyso-sulfatide. Presentation of lyso-sulfatide is inhibited in the presence of primaquine, concanamycin A, monensin, cycloheximide, and an inhibitor of microsomal triglyceride transfer protein but remains unchanged following treatment with brefeldin A. Wortmannin-mediated inhibition of lipid presentation indicates an important role for the PI-3kinase in mCD1d trafficking. Our data collectively suggest that weak CD1d-binding self-glycolipid ligands such as lyso-sulfatide can be presented via the secretory and endosomal compartments. Thus this study provides important insights into the exogenous self-glycolipid presentation to CD1d-restricted T cells.

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Section: Involvement Of Secretory and Endosomal Compartments Inmentioning

confidence: 99%

Involvement of Secretory and Endosomal Compartments in Presentation of an Exogenous Self-Glycolipid to Type II NKT Cells

Roy

Maricic

Khurana

et al. 2008

The Journal of Immunology

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“…There was no signi®cant effect of CD1a, -b and -c 390 M. Ulanova et al 5 /ml) to tetanus toxoid (TT) (1 mg/ml) under the same conditions described in the legend to Fig. 1, except that a suboptimal concentration of anti-major histocompatibility complex (MHC) class II antibody (1.25 mg/ml) was used.…”

Section: Cd1 Moabs Do Not Affect Responses In Mlc or To Superantigenimentioning

confidence: 99%

Participation of CD1 Molecules in the Presentation of Bacterial Protein Antigens in Humans

Ulanova¹,

Tarkowski

Hahn-Zoric³

et al. 1999

Scand J Immunol

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Human CD1 molecules, expressed on the surface of professional antigen-presenting cells (including dendritic cells, Langerhans' cells, B cells and activated monocytes) are structurally homologous to major histocompatibility complex (MHC) class I and class II molecules. CD1b and CD1c have been shown to present nonpeptide bacterial antigens to T cells. We hypothesized that CD1 molecules may also be involved in the presentation of bacterial protein antigens. Human peripheral blood mononuclear cells (PBMC) were exposed to two medically important proteins, tetanus toxoid (TT) and puri®ed protein derivative (PPD), with and without murine monoclonal antibodies (MoAbs) speci®c for CD1a, CD1b and CD1c. All the MoAbs substantially inhibited the proliferative responses of PBMC to TT and PPD. Simultaneous interaction of CD1 and MHC class II molecules was even more inhibitory to these antigen-speci®c proliferative responses. In contrast, neither mixed lymphocyte reaction nor superantigen and mitogenic responses were affected by CD1-speci®c antibodies, indicating a certain restriction pattern in antigen presentation. Our ®ndings suggest that, besides MHC class I and II molecules, there is a family of nonpolymorphic cell surface molecules that is able to present certain bacterial protein antigens to T cells.

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“…However, in contrast to the MHC-lineage, CD1 proteins are nonpolymorphic and feature a deep and hydrophobic binding groove, ideally suited for binding self-and foreign lipids, glycolipids, lipopeptides and other hydrophobic molecules (8). In humans, the various CD1 isoforms are divided into group 1 (CD1a, CD1b, CD1c, and CD1e) and group 2 (CD1d) based on sequence similarities (9), but mice only express group 2 CD1d. Whereas group 1 CD1 are recognized by conventional ␣␤ ϩ or ␥␦ ϩ T cells, the main population of group 2 CD1 molecules activate NKT cells (10), which express both an ␣␤ ϩ TCR and typical markers, such as NK1.1.…”

mentioning

confidence: 99%

Structural Characterization of Mycobacterial Phosphatidylinositol Mannoside Binding to Mouse CD1d

Zajonc

Ainge²,

Painter³

et al. 2006

The Journal of Immunology

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Mycobacterial phosphatidylinositol tetramannosides (PIM4) are agonists for a distinct population of invariant human (Vα24) and mouse (Vα14) NKT cells, when presented by CD1d. We determined the crystal structure at 2.6-Å resolution of mouse CD1d bound to a synthetic dipalmitoyl-PIM2. Natural PIM2, which differs in its fatty acid composition is a biosynthetic precursor of PIM4, PIM6, lipomannan, and lipoarabinomannan. The PIM2 headgroup (inositol-dimannoside) is the most complex to date among all the crystallized CD1d ligands and is remarkably ordered in the CD1d binding groove. A specific hydrogen-bonding network between PIM2 and CD1d orients the headgroup in the center of the binding groove and above the A′ pocket. A central cluster of hydrophilic CD1d residues (Asp153, Thr156, Ser76, Arg79) interacts with the phosphate, inositol, and α1–α6-linked mannose of the headgroup, whereas additional specificity for the α1- and α2-linked mannose is conferred by Thr159. The additional two mannoses in PIM4, relative to PIM2, are located at the distal 6′ carbon of the α1-α6-linked mannose and would project away from the CD1d binding groove for interaction with the TCR. Compared with other CD1d-sphingolipid structures, PIM2 has an increased number of polar interactions between its headgroup and CD1, but reduced specificity for the diacylglycerol backbone. Thus, novel NKT cell agonists can be designed that focus on substitutions of the headgroup rather than on reducing lipid chain length, as in OCH and PBS-25, two potent variants of the highly stimulatory invariant NKT cell agonist α-galactosylceramide.

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Two classes of CD1 genes

Cited by 249 publications

References 21 publications

Involvement of Secretory and Endosomal Compartments in Presentation of an Exogenous Self-Glycolipid to Type II NKT Cells

Involvement of Secretory and Endosomal Compartments in Presentation of an Exogenous Self-Glycolipid to Type II NKT Cells

Participation of CD1 Molecules in the Presentation of Bacterial Protein Antigens in Humans

Structural Characterization of Mycobacterial Phosphatidylinositol Mannoside Binding to Mouse CD1d

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