CD85d ILT4 (immunoglobulin-like transcript-4), LIR2 (leukocyte immunoglobulin-like receptor-2), LILRB2 (leukocyte immunoglobulin-like receptor, subfamily B with TN and ITIM domains), MIR10
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Myeloid Cell
Dendritic Cell
NK Cell
T Cell
Macrophage
Monocyte
B Lymphocyte
110 / 110

Expression
CD85d is expressed on NK and T cell subsets, monocytes, macrophages, some dendritic cells, B lymphocytes, myeloid cells and weakly on granulocytes.  In vitro expression is not on Lin-HLA-DR+CD11c- or Lin-HLA-DR+CD11c+ fresh blood dendritic cells.

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

CD85d is a single-pass type-1 glycoprotein.  It contains a 440 aa extracellular domain which contains 4 Ig-like C2-type domains, a 21 aa transmembrane and a 116 aa long cytoplasmic domain contains 3 ITIM sequences.  The ILT/LIR family is a member within the Ig gene superfamily.

MOLECULAR MASS

POST-TRANSCRIPTIONAL MODIFICATION:

Alternative splicing yields 2 different isoforms.

POST-TRANSLATIONAL MODIFICATION: No information.


Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD85d:

CD85d binds HLA class I and the trophoblast-specific, nonclassic class I molecule HLA-G1.

Function
CD85d is an inhibitory receptor for the MHC class I molecule including HLA-A, -B, -G1 and -E.  CD85d is involved in the suppression of NK-mediated cytotoxicity.  Cytoplasmic ITIMs recruit and activate protein tyrosine phosphatases SHP-1 and/or SHP-2 that acts inibibitory signal effector molecules.  Antigen presenting cells expressing CD85k and CD85d appear to be crucial to the generation ofCD8+ suppressor T cells and CD4+ regulatory cells.  CD40 stimulated chemokine and cytokine production in monocytes is modulated by CD85j and CD85d after engagement by class I molecules.
   
BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD85j IN INTACT ANIMAL

The trophblast-specific HLA-G1 protein binds CD85j and CD85d.  This interaction possibly contributes to maternal tolerance of the fetus by inhibiting maternal leukocytes.



Comments
Previously, the ILT family was clustered together as CD85.  Recently subclassifications have been given to individual members listed as CD85a - CD85m.  Ig-like transcripts (ITLs) and leukocyte Ig-like transcripts (LIRs) are structurally and functionally related transmembrane glycoproteins.  The receptors are divided into 2 groups of inhibitory and activating receptors according to the nature of their transmembrane and cytoplasmic regions.  Receptors with a long cytoplasmic tail, CD85a (ILT5/LIR3), CD85c (LIR8), CD85d (ILT4/LIR2), CD85j (ILT2/LIR1) and CD85k (ILT3/LIR5), contain one or more intracytoplasmic ITIMs which recruit and activate protein tyrosine phosphates SHP-1 and/or SHP-2.  Receptors with a short tail, CD85b (ILT8), CD85f (ILT11), CD85g (ILT7), CD85h (ILT1/LIR7) and CD85i (LIR6a) lack ITIMs and contain a positively charged aa residue, arginine or lysine, in their transmembrane domain which is necessary for association with ITIM-containing polypeptides like FcRg chain.  CD85l (ILT9) and CD85m (ILT10) bind the FcRg chain.  Phosphorylated ITAMs recruit the protein tyrosine kinases Syk and ZAP70.  One exception to these transmembrane receptors is CD85e (ILT6/LIR4) which has no transmembrane or cytoplasmic domains and is probably soluble.                     

MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD85d: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD85d: No information.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene10288Q8N423
Antibodies

Revised June 25, 2008


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