CD85j ILT2 (immunoglobulin-like transcript-2), MIR7, LIR1 (immunoglobulin-like receptor-1), LILRB1(leukocyte immunoglobulin-like receptor, subfamily B with TM and ITIM domains, member 1)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Myeloid Cell
Monocyte
Dendritic Cell
B Lymphocyte
Plasma Cell
Lymphoid Cell
T Cell
Leukemia cell
110 / 110

Expression
CD85j is expressed on myeloid and lymphoid cells.  In the myeloid lineages, expression is on monocytes and dendritic cells.  It is expressed on T cells, on mature circulating B lymphocytes and plasma cells. CD85j is expressed on Lin-HLA-DR+CD11c- fresh blood dendritic cells but only on a subpopulation of Lin-HLA-DR+CDc+.  Monocyte derived dendritic cells, MoDC, express CD85j.  In vitro generated dendritic cells derived from CD34+ cells express CD85j but at lower levels than expressed by MoDC.  CD85j is expressed strongly in acute lymphoblastic leukemia (ALL), most pre-B ALL, most B cell CLL, B-NHL and all hairy cell leukemias.  It is expressed by myeloid leukemia cells and some CD30+ CTCL.

Structure
MOLECULAR FAMILY NAME: Belongs to the immunoglobulin supergenefamily.

CD85j is a single-pass type-1 650 aa transmembrane glycoprotein.  It contains a 23 aa signal peptide, a 438 aa extracellular domain which contains 4 Ig-like C2-type domains, a 21 aa homologous transmembrane and a long 168 aa cytoplamic tail containing 4 ITIM sequences.  The ILT/LIR family is a member within the Ig gene superfamily.

MOLECULAR MASS

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 3 different isoforms.

POST-TRANSLATIONAL MODIFICATION

The phosphorylated ITIM can bind the SH2 domain of several SH2-containing phosphates.

Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD85j

CD85j binds a broad range of HLA-A and -B molecules, some HLA-C molecules, the trophoblast-specific, nonclassic class I molecule HLA-G1, and the human cytomegalovirus UL18 protein.

Function
CD85j is involved in the suppression of NK-mediated cytotoxicity.  CD85j is an inhibitory receptor for MHC class I molecules including HLA-A, -B, -G1 and -E.  Ligation with these molecules induces an inhibitory signal via recruitment of SHP-1 phosphatase. CD85j has been shown to downregulate antigen-specific cytolytic activity of CD8+ T cells and inhibits responses to recall antigens by CD4+ T cells.  Co-engagement of CD85j with the B cell receptor inhibts Ca2+ mobilization triggered via the BCR suggesting CD85j modulates the threshold of antigen-mediated B cell activation.  CD85j mediates inhibition of NK cell mediated cytotoxicity.  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

Soluble CD85j binds UL18, a class I molecule expressed by the human cytomegalovirus.  This binding has the potential to block leukocyte activation and prevent an anti-viral response.  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 CD85j: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD85j: No information.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene10859Q8NHL6
Antibodies

Revised June 25, 2008


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