CD1c M241, R7
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Lineage Restricted Molecule
Type 1 glycoprotein
Cortical Thymocyte
Langerhans Cell
Dendritic Cell
Myeloid Leukemia
B Cell
T Lymphocyte
Thymocyte
43 / 43

Expression
CD1c is expressed on cortical thymocytes and with 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.  CD1c is expressed by a subset of peripheral blood B cells.  However, a proportion of B cell malignancies express CD1c isotypes.  Less levels of CD1c are present on Langerhans cells (LC).  After migration from epidermis or on dendritic cells from the dermis, there is a high expression of CD1c. CD1c is detected in myeloid leukemias.  These molecules are induced on monocytes by treatment with the granulocyte-macrophage colony stimulating factor (GM-CSF) alone or by GM-CSF plus IL-4.


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

CD1c is a single-pass type-1 a chain glycoprotein.  It contains an extracellular domain which contains 3 domain, α1, α2 and α each 90 aa, 3 potential N-glycosylation sites in domains α1 and α2, a transmembrane domain and a short cytoplasmic domain containing  a tyrosine-based motif YXXZ which is essential for access to late endosomes and lipid binding.  It is non-covalently associated with b2 microglobulin  and has structural similqrities to MHC class I molecules. 

MOLECULAR MASS
Cell Type Unreduced Reduced
Thymocytes 43 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.  In CD1c a similar 3 band pattern was described in thymus and in the transfected cell line.  The unspliced isoform is homologous to the secreted form of CD1a.  A 2nd product corresponds to the "correctly" spliced membrane form. The 3rd product is slightly different from its equivalent of CD1a. Resting peripheral blood mononuclear cells (PBMC) lack the unspliced product but it is detected after stimulation with phythohemagglutinin (PHA).  These results suggest that like CD1a, CD1c is also under development control.

POST-TRANSLATIONAL MODIFICATION

Potential N-linked glycosylation sites are 3 in CD1c.  Differences between native and deglycosylated a chains suggests 3 oligosaccharide side chains of average size in CD1c.

Ligands
LIGAND AND MOLECULES ASSOCIATED WITH CD1c

Some T cells recognize 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 that seen for class I and resembles class II peptide binding.



Function
CD1c is associated with β2 microglobulin and non-peptide Ag presentation.  Antigen presentation on T cells seems to be independent of endosomal acidification despite its location to endosomal compartments and exocytosis is via an atypical pathway that does not require early endosomes.  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 CD1c 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 CD1c: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD1c: No information.

ADDITIONAL INSIGHTS

CD1c is homologous to histocompatibility antigens but is not genetically linked to the histocompatibility locus.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 911P29017
Antibodies
L161   View Reactivity

Revised June 25, 2008


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