CD1d R3
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Lineage Restricted Molecule
Type 1 glycoprotein
Cortical Thymocyte
Monocyte
Thymus
T Lymphocyte
Epithelial Cell
Lymphocyte
Small intestine
38 / 38

Expression
CD1d is expressed on cortical thymocytes and with a less intensity on CD4+ and CD8+ thymocytes.  CD1 is absent on mature peripheral blood T cells but intracytoplasmic expression is detected on activated T lymphocytes.  The molecules are induced on monocytes by treatment with the granulocyte-macrophage colony stimulating factor (GM-CSF) alone or by GM-CSF plus IL-4.  CD1d gene products are expressed at low levels in the thymus.  Immunoperoxidase staining with an anti-mouse CD1, which cross reacts with the human CD1d, demonstrated the cytoplasmic expression of this molecule on most epithelial cells in the large and small intestine.


Structure
MOLECULAR FAMILY NAME:  Belongs to the immunoglobulin supergene family.

CD1d is a single-pass type-1 a chain glycoprotein. It contains an extracellular domain which contains 3 domains, α1, α2 and α3 each 90 aa, 4 potential N-glycosylation sites in domains α1 and α2, a tramsmembrane domain and a short cytoplasmic domain containing a tyrosine-based motif YXXZ essential for access to late endosomes and lipid binding.  It is non-covalently associated with b2 microglobulin and has structural similarity to MHC class I molecules. 

MOLECULAR MASS 
Cell Type Unreduced Reduced
Thymocytes 43 kDa-49 kDa

POST-TRANSCRIPTIONAL MODIFICATION

The alternative splicing pattern is tissue specific and gives rise to membrane attached and soluble forms. Multiple splicing patterns have been found for all CD1 transcripts except for CD1b.  The CD1d-transfected cell line and thymocytes showed the presence of 1 spliced membrane product.  This product is absent on resting peripheral blood mononuclear cells (PBMC) but was induced after 72 hours of phythohemagglutinin (PHA) activation.  CD1d expression on intestinal epithelial cells has also revealed different alternatively spliced products.  There is 1 transcript which terminates in a cryptic polyadenylation site in the intron between a2 and a3 domains exons.  A 2nd transcript deletes the TM region exon, and a 3rd deletes the a3 domains exon.  It is currently unknown whether this transcript encodes functional proteins.

POST-TRANSLATIONAL MODIFICATION

Potential N-linked glycosylation sites are 4 in CD1d.

Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD1d

Some T cells recognize an antigen in a CD1-restricted manner.  Mouse NK1+ T lymphocytes which have a restricted TCR repertoire recognize murine CD1, although there is conflicting data.  A recombinant form of the murine CD1 binds synthetic peptides with micromolar affinities.  It showed a preference for longer peptides than seen for class I and resembles class II peptide binding.



Function
CD1d associates with β2 microglobulin and non-peptide Ag presentation and is involved in the positive selection of sublineage of NKT cells.  CD1s have been demonstrated to restrict T-cell responses to non-peptide lipid and glycolipid antigens.  CD1 molecules could be involved in the delivery of signals for lymphocyte activation.  Some anti-CD1 mAbs produced inhibition of bacterial superantigen thymocytes proliferation.  On PBMC, depending on the epitope recognized by the mAb, an inhibitory or enhanced effect on the proliferative response to the phosphokinase C (PKC) activator phorbol myristate acetate (PMA) has been observed.  The expression of CD1 molecules on thymocytes has been related to a role in thymic T-cell development.  NK1+ cells a subset of T cells found in high frequencies in the mature compartment of the mice thymus are involved in the development of NK cells. These cells, found in high frequencies in bone marrow and liver, have CD1 molecules as their ligand.  It has been postulated that through their NK-like activity, the liver is actively involved in the peripheral cell deletion of T cells arriving from the intestine through the portal vein.  By this mechanism, these cells may be involved in the induction of oral tolerance.

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD1d IN INTACT ANIMAL: No information.

Comments

CD1 genes, except CD1b, are transcribed in the same direction and all lack classical promoter elements.

MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD1d: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD1d: No information. 

ADDITIONAL INSIGHTS

CD1d is homologous to histocompatibility antigens but is not genetically linked to the histocompatibility locus.



Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 912P15813
Antibodies
NOR3.2   View Reactivity

Revised June 25, 2008


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