Lipid protein interactions: the assembly of CD1d1 with cellular phospholipids occurs in the endoplasmic reticulum.
(2002)
Journal - Journal of immunology (Baltimore, Md. : 1950) (United States )
Abstract :
CD1d1 is a member of a family of lipid Ag-presenting molecules. The cellular ligands associated with CD1d1 were isolated and characterized by biochemical means as an approach to elucidate the mechanism by which CD1 molecules assemble in vivo. Natural ligands of mouse CD1d1 included cellular phosphatidylinositol and phosphatidylinositol-glycans that are synthesized in the endoplasmic reticulum. Further biochemical data revealed that the two CD1d1 mutants, one defective in recycling from-and-to the plasma membrane and the other in efficiently negotiating the secretory pathway, associated with phosphatidylinositol. Thus phosphatidylinositol associated with CD1d1 in the early secretory pathway. Phosphatidylinositol also associated with CD1d1 in Pig-A-deficient cells that are defective in the first glycosylation step of glycosylphosphatidylinositol biosynthesis. Moreover, cellular phosphatidylinositol-glycans are not Valpha14Jalpha15 natural T cell Ags. Therefore, we predict that cellular lipids occlude the hydrophobic Ag-binding groove of CD1 during assembly until they are exchanged for a glycolipid Ag(s) within the recycling compartment for display on the plasma membrane. In this manner, cellular lipids might play a chaperone-like role in the assembly of CD1d1 in vivo, akin to the function of invariant chain in MHC class II assembly.
| ISSN : | 0022-1767 |
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| Mesh Heading : | Animals Antigen Presentation Antigens, CD1 Antigens, CD1d Dolichol Phosphates Endoplasmic Reticulum Glycosylphosphatidylinositols Humans Intracellular Fluid K562 Cells Ligands Mannose Mice Phosphatidylethanolamines Phosphatidylinositol Diacylglycerol-Lyase Phosphatidylinositols Phospholipids Polysaccharides Tumor Cells, Cultured Type C Phospholipases metabolism enzymology deficiency genetics metabolism immunology metabolism metabolism metabolism metabolism metabolism metabolism |
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| Mesh Heading Relevant : | metabolism immunology metabolism metabolism |
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Lipid–protein interactions: Biosynthetic assembly of CD1 with lipids in the endoplasmic reticulum is evolutionarily conserved
(2004)
Journal - PNAS
Abstract :
The CD1 family consists of lipid antigen-presenting molecules,which include group I CD1a, CD1b, and CD1c and group II CD1dproteins. Topologically, they resemble the classical peptideantigen-presenting MHC molecules except that the large, exclusivelynonpolar and hydrophobic, antigen-binding groove of CD1 hasevolved to present cellular and pathogen-derived lipid antigensto specific T lymphocytes. As an approach to understanding thebiochemical basis of lipid antigen presentation by CD1 molecules,we have characterized the natural ligands associated with mouseCD1d1 as well as human CD1b and CD1d molecules. We found thatboth group I and II CD1 molecules assemble with cellular phosphatidylinositol(PI), which contains heterogeneous fatty acyl chains. Further,this assembly occurs within the endoplasmic reticulum. Becausethe structures of the antigen-binding grooves of CD1a and CD1cclosely resemble those of CD1b and CD1d, we conclude that theassembly of CD1 molecules with PI in the endoplasmic reticulumis evolutionarily conserved. These findings suggest that PIplays a chaperone-like role in CD1 assembly, possibly to preservethe integrity of the antigen-binding groove until CD1 bindsantigenic lipids in the endocytic pathway. J.-J.P. and S.-J.K. contributed equally to this work. Present address: Departments of Medicine and Microbiology/Immunology,University of California, San Francisco, CA 94143.¶ Present address: Department of Microbiology and Immunology,Albert Einstein College of Medicine, Bronx, NY 10461.
Lipid Protein Interactions: The Assembly of CD1d1 with Cellular Phospholipids Occurs in the Endoplasmic Reticulum1
(2002)
Journal - The Journal of Immunology
Abstract :
CD1d1 is a member of a family of lipid Ag-presenting molecules.The
cellular ligands associated with CD1d1 were isolated andcharacterized
by biochemical means as an approach to elucidatethe mechanism by which
CD1 molecules assemble in vivo. Naturalligands of mouse CD1d1 included
cellular phosphatidylinositoland phosphatidylinositol-glycans that are
synthesized in theendoplasmic reticulum. Further biochemical data
revealed thatthe two CD1d1 mutants, one defective in recycling
from-and-tothe plasma membrane and the other in efficiently
negotiatingthe secretory pathway, associated with
phosphatidylinositol.Thus phosphatidylinositol associated with CD1d1
in the earlysecretory pathway. Phosphatidylinositol also associated
withCD1d1 in Pig-A-deficient cells that are defective
in the firstglycosylation step of glycosylphosphatidylinositol
biosynthesis.Moreover, cellular phosphatidylinositol-glycans are not
V14J15natural T cell Ags. Therefore, we predict that cellular
lipidsocclude the hydrophobic Ag-binding groove of CD1 during assembly
untilthey are exchanged for a glycolipid Ag(s) within the recycling
compartmentfor display on the plasma membrane. In this manner,
cellularlipids might play a chaperone-like role in the assembly of
CD1d1in vivo, akin to the function of invariant chain in MHC classII
assembly.