CD158b1 KIR2DL2 (killer cell immunoglobulin-like receptor, 2 domains, long cytoplasmic tail, 2), NKAT6, CD158k
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
NK Cell
T Cell

50 / 50
58 / 58

Expression
CD158b1 is expressed on most NK and some T cell subsets.  Expression on individual NK cells is complex and  may express several members of the KIR family.  The repertoire of KIR molecules varies among NK cells and is not determined solely by the HLA haplotypes.



Structure
MOLECULAR FAMILY NAME:  Belongs to the immunoglobulin gene superfamily.

CD158b1 is a single-pass type-1 348 aa transmembrane glycoprotein.  It contains an extracellular 2 Ig-like C2-type domains (D1 and D2) which preceeds a 17 aa proline-serine-rich stem that links the Ig domain to the transmembrane, a transmembrane domain and a 76-114 aa long cytoplasmic domain of the inhibitory form p58.1 with 2 ITIMS.  There are 4 members that have been characterized at the molecular level with 224 aa in the extracellular region of all 4 forms.  The crystal structure of CD158b1 reveals a similarity with the structure of the hematopoietic family.  

MOLECULAR MASS
Cell Type Unreduced Reduced Comment
NK cells 58 kDa 58 kDa 42 kDa backbone [inhibiting form (p58.1)]
NK cells 50 kDa 50 kDa 36 kDa backbone [activating form (p50.1)]

POST-TRANSCRIPTIONAL MODIFICATION:

Alternative splicing yields 2 different isoforms.

POST-TRANSLATIONAL MODIFICATION

Several N-linked glycosylation sites and 2 tyrosine phosphorylation sites in the long cytoplasmic tails are only in the inhibitory form CD158b1.



Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD158b1

CD158b1 binds HLA-C molecules with Asn80 and Ser77.  HLA binds Cw1, Cw3, Cw7 and Cw8.



Function
CD158b1 is involved in the suppression of NK mediated cytotoxicity and prevents cell lysis.  KIR with ITIM sequences in the cytoplasmic domain inhibit NK and CTL mediated lysis against certain targets expressing an appropriate MHC class I ligand.  In addition, interactions between KIR on NK or T cells and MHC class I on antigen-presenting cells can inhibit cytokine production.  In contrast, T or NK cells expressing KIR without an ITIM such as KIR2Ds may enhance cytolysis against target cells expressing an appropriate MHC class I ligand.  However, inhibitory KIR can prevent stimulation by an activating KIR if the potential target or antigen presenting cell also expresses a ligand of the inhibitory KIR.  CD158b1 regulates the NK cell mediated cytolytic activity upon interaction with the appropriate HLA-C alleles, recognizing these groups of HLA class 1 allotypes rather than individual MHC class I peptide complexes.

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD158b1 IN INTACT ANIMAL

In murine models, inhibitory NK cell receptors that are functional homologs of human KIR (eg. the Ly49 receptors) regulate rejection of bone marrow grafts from semi-allogeneic or allogeneic donors.  Expression of a human KIR transgene controls NK mediated rejection of allogeneic bone marrow grafts.  There is also evidence that KIR may be expressed on melanoma specific CTL and regulate their ability to kill these tumors. 


Comments
Killer cell immunoglobulin (Ig)-like receptors (KIR), also called killer cell inhibitory receptors, are glycoproteins expressed in natural killer (NK) cells and some T cells.  The KIR family is estimated to include about 11 genes.  Some members of the KIR family bind to certain HLA class I deficient cell lines.  Ligation of such KIR by HLA class I molecules on target cells results in inhibition of the NK or T cell cytotoxic activity.  The inhibition could be disrupted by antibodies against membrane glycoproteins on NK cells that recognized HLA- and HLA-C.  Inhibitory KIRs are found in 3 distinct isoforms.  KIRs that recognize HLA-C are usually monomeric glycoproteins of about 58 kDa with 2 Ig-like domains (KIR2D).  KIRs that are reactive with HLA-B are approximately 70 kDa monomeric glycoproteins with 3 Ig-like domains (KIR3D).  The KIR family is further subdivided into forms with short and long intracytoplasmic tails.  The 1st and 2nd Ig domains in KIR2D are closely related in aa sequence to the 2nd and 3rd Ig domains in KIR3D. These 2 related Ig domains are called D1 and D2, respectively.  D0 is the 1st Ig domain in KIR3D.  KIR members vary in the length of the cytoplasmic tails.  Most of the long cytoplasmic tails, KIR2DL and KIR3DL, deliver an inhibitory signal and carry 2 immunoreceptor tyrosine-based inhibition motifs (ITIM) which recruit and activate protein tyrosine phosphates, SHP-1 and or SHP-2.  Other receptors, of about 50 kDa, with short cytoplasmic regions (KIR2DS and KIR3DS) are truncated before the 1st ITIM causing them to have no ITIMs.  They are are connected to a transmembrane region which includes a lysine residue and can activate NK or T cell responses.  The short tail associates with a disulfide dimer of 14 kDa. phosphoproteins called DAP12 which is also known as killer activating protein (KARAP).

MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD158b1: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD158b1: No information.

ADDITIONAL INSIGHTS

CD158a and CD158b includes 2 different molecules, p58.1 and p50.1, with divergent functional effects like inhibition and activation, respectively, which are presumably encoded by different genes in the same family.



Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 3803P43627
Antibodies

Revised June 25, 2008


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