CD161  KLRB1(killer cell lectin-like receptor subfamily B, member 1), NKR-P1A
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Lineage Restricted Molecule
Type 2 glycoprotein
NK Cell
Peripheral blood
Thymocyte
Cytokine
T Cell
Liver
40 / 40
44 / 44

Expression
CD161 is expressed on most NK cells and a subset of CD4+ and CD8+ T cells.  CD161 is preferentially expressed on T cells with a 'memory' phenotype in adult peripheral blood.  CD161 is also found on a subset of thymocytes and fetal liver T cells.  In humans, CD161 is present on ~90% of NK cells, ~25% of T cells on both CD4 and CD8 cells, and a subset of very immature thymocytes.  In the rat, CD161 is found on all NK cells at high levels and at low levels on most neutrophils and a subset of T cells.  In the mouse CD161 is expressed on all NK cells as well as subsets of thymocytes and peripheral T cells.  Transcripts of all 3 mouse genes have been detected in a single cell, suggesting that multiple CD161 molecules can be expressed simultaneously by NK cells.  T lineage cells expressing CD161 form a functionally distinct group, termed 'natural T' or NT cells, and are characterized by expression of a TCR with an invariant a chain, Va 14-Ja 281a , restriction CD1, and rapid expression of cytokines including IL-4, IL-5 and IL-10 upon activation.  Several common laboratory strains of mice like BALB/c, appear not to express CD161
molecules.



Structure
MOLECULAR FAMILY NAME: Belongs to the C-type lectin superfamily.

CD161 is a disulfide-bonded homodimeric single-pass type-2 217 aa glycoprotein.  It contains an 158 aa extracellular domain which contains a C-type lectin domain and a potential N-linked carbohydrate and deglycosylation N-glycosidase F, a 29 aa transmembrane domain and a 38 aa cytoplasmic domain.  Human CD161 is an orthologue of the mouse and rat CD161 genes. 

The NKR-P1 family members are structurally related to several other proteins encoded within the NK gene complex, including Ly-49 proteins, CD69, CD94 and NKG2.  The NKR-P1 locus lies 0.41 cM distal to the Ly-9 locus on mouse chromosome 6.  Human NKR-P1A may have a monomeric form as well.  Cloned 3 distinct genes have been identified in the mouse and there are preliminary reports of at least 4 distinct genes existing in the rat but only 1 gene has been identified thus far in humans.  The 3 mouse proteins show a 73%-87% aa identity with each other, a 61%-74% aa identity with the rat NKR-P1A, and a 46%-47% aa identity with the human NKR-P1A.  The rat NKR-P1A is most closely related to the mouse NKR-P1A, but it is not clear which mouse gene is the homologue of human NKR-P1A.  There is evidence for alternatively spliced mouse NKR-P1A transcripts.  The cytoplasmic domains contains conserved potential Thr-YXXL and Ser-SPXSLXXDXC phosphorylation sites.

MOLECULAR MASS
Cell Type Undreduced Reduced
NK cells and T cells ~80 kDa ~40 kDa

POST-TRANSCRIPTIONAL MODIFICATION

Northern blot analysis indicates a transcript of ~0.9 kb.  Splice isoforms within the coding region of CD161 have not been identified.

POST-TRANSLATIONAL MODIFICATION

Treatment of CD161 proteins with N-glycanase reduces the molecular mass from ~40 kDa to ~26 kDa, consistent with the presence of N-linked oligosaccharides.  O-linked saccharides have not been detected.

Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD161

The C-type lectin domain rat CD161 has been reported to bind to a variety of carbohydrate structures but the biological relevance of these interactions is under re-evaluation.  CD161 binds MHC class I.




Function
The function of CD161 is undefined but may play a role in NK cell mediated cytotoxicity function.  Monoclonal antibodies against CD161 have been reported to either augment or inhibit NK cell-mediated cytotoxicity against certain Fc-receptor bearing targets and to induce immature thymocyte proliferation.  Studies in the rat suggest that the CD161 molecule functions as a specific receptor for certain NK cell targets, with a ligation of CD161 activating NK cell killing.  T cells expressing CD161 are capable of cytotoxicity following culture in IL-2. Although a single human CD161 gene has been identified, the mouse has three separate genes which encode for stimulatory and inhibitory products.  In the mouse,. antibodies to CD161 can activate NK cells and block NK cell killing of target cells.  However, certain common mouse strains appear to not express CD161 gene products and yet exhibit normal NK cell function.  CD161 has also been implicated in the NK cell function in humans but studies with antibodies indicate that receptor ligation may activate or inhibit lytic function in different NK cell clones.  CD161 is not essential for the development of natural T cells since this cell population is unchanged in mice lacking CD161.

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD161 IN INTACT ANIMAL: No information.

Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD161: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD161: No information.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 3820P12918
Human-NKRI38700U11276
Mouse-NKRA46467P27811M77676
Mouse-NKRB46467P27812M77677
Mouse-NKRC46467P27814M77678
Rat-NKRA35917P27471M62891
Antibodies

Revised June 25, 2008


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