CD1a R4, HTA1, T6/leu-6 
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Lineage Restricted Molecule
Type 1 glycoprotein
Thymocyte
Monocyte
Dendritic Cell
Langerhans Cell
T Lymphocyte
Myeloid Leukemia
B Cell
Cytokine
49 / 49

Expression
CD1a 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.  CD1a is not detected on normal B cells.  However a proportion of B cell malignancies express CD1a isotypes.  High levels of CD1a are present on Langerhans cells (LC).  CD1 antigens are also expressed on some dendritic cells and cytokine-activated monocytes.  CD1a is not expressed on intestinal epithelium.  Different CD1 molecules can be co-expressed on the same cell.  CD1a is detected in T cell myeloid leukemias and in various other tissues.  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.

CD1a is a single-pass type-1 a chain 1 glycoprotein.  It contains an extracellular domain which contains 3 domains, α1, α2 and α3 each 90 aa, 3 potential N-glycosylation sites in domains α1 and α2, a transmembrane domain and a short cytoplasmic domain but it lacks the tyrosine-based motif.  CD1a has structural simaritities to MHC proteins and forms heterodimers and is non-covalently associated with b2 microglobulin. 

MOLECULAR MASS
Cell Type Unreduced Reduced
Thymocytes 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.  CD1a, the most abundant mRNA, contains the intron between the a3 and the transmembrane (TM) domains, resulting in a stop codon just downstream of the a3 domain an unspliced transcript.  Biochemical studies have demonstrated that a secretory form of CD1a is synthesized from this transcript.  The 2nd product represents the membrane isoform.  The 3rd transcript corresponds to a product where the a3 domain is spliced to the middle of the TM domain.  The resulting product does not include most of the hydrophobic segment required for membrane attachment and this has been postulated as a possible cytoplasmic protein.  On thymocytes, only the membrane isoform is detected.   Activated peripheral blood lymphocytes express a particular pattern of alternative splicing different from the one found in thymus and a transfected cell line.

POST-TRANSLATIONAL MODIFICATION

Potential N-linked glycosylation sites are 3 in CD1a.  Differences between native and deglycosylated a chains suggests 4 oligosaccharide side chains of average size in CD1a.

Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD1a

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 shows a preference for longer peptides than seen for class I and resembles class II peptide binding. 



Function

CD1a associates with β2 microglobulin and non-peptide Ag presentation.  CD1a may play a role in thymic T cell development and its presence on activated T cells suggests it may be involved in regulating T cell responses.  As suggested by its similarity to MHC antigens and as inferred above, there is evidence for roles in presentation of lipid and peptides to T cells.  CD1 has a role in positive selection of NK1+ T cells.  The pathway for presentation of exogenous antigen by CD1 is different from that for MHC Class I and II.  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 peripheral blood mononuclear cells (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 CD1a IN INTACT ANIMALS: 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 CD1a: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD1a: No information.

ADDITIONAL INSIGHTS

CD1a is related to histocompatibility antigens but is not genetically linked to the histocompatibility locus

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 909P06126NM-001763
MouseS01297P11609X13170
RatD26439
Antibodies
B17.20.9   View Reactivity
BL6   View Reactivity
M-T102   View Reactivity
NA1/34   View Reactivity

Revised June 25, 2008


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