Disease relevance of Cd244

• In keeping with this, male 2B4(-/-) mice showed enhanced ability to reject CD48(+) melanoma cells [1].
• Targeted disruption of the 2B4 gene in mice reveals an in vivo role of 2B4 (CD244) in the rejection of B16 melanoma cells [1].
• RESULTS: Activation of 2B4 or CD48 resulted in a five-fold reduction in tumor metastasis [2].
• Moreover, activation of eosinophils via 2B4 induced eosinophil-mediated cytotoxicity toward two malignant cell lines, i.e., mouse mastocytoma P815 and EBV-infected 721.221 B cell lines [3].
• We speculate that evolutionary pressure from viral infections, possibly EBV, might have led to the emergence of this association and activating function of 2B4 in humans [4].

High impact information on Cd244

• A putative T-cell receptor gene was isolated from the DNA of the helper hybridoma, 2B4 . Analysis of the sequence components of this rearranged gene indicates the presence of separate variable (V), diversity (D) and joining (J) region elements analogous to those of heavy-chain immunoglobulins [5].
• FcRgamma signaling is also defective, resulting in a loss of collagen-induced platelet aggregation, mast cell FcepsilonR function, and NK cell FcgammaRIII and 2B4 function [6].
• Like SAP, EAT-2 was associated with the SLAM-related receptor 2B4 in NK cells [7].
• In keeping with earlier reports that studied human NK cells, we showed that SAP was necessary for the ability of 2B4 to trigger cytotoxicity and IFN-gamma secretion [8].
• These findings reveal a novel role for 2B4 as a non-major histocompatibility complex binding negative regulator of NK cells [9].

Chemical compound and disease context of Cd244

• LNCaP lineage-derived human prostate cancer cell lines C4-2 and C4-2B4 acquire androgen independence and osseous metastatic potential in vivo [10].

Biological context of Cd244

• The gene encoding C9.1 antigen was linked to the Akp1 isozyme locus on chromosome 1 close to the 2B4 gene [11].
• 2B4 (CD244)-CD48 interactions provide a novel MHC class I-independent system for NK-cell self-tolerance in mice [12].
• Functional impairment of NK cells in the absence of 2B4/CD48 interactions was accompanied by defective calcium signaling, suggesting that the early signaling pathway of NK receptors is inhibited [13].
• The biological function of 2B4, a CD48-binding molecule expressed on T cells with an activation/memory phenotype, is not clear [14].
• This association is independent of both 2B4 phosphorylation and the cytoplasmic tail of 2B4 [15].

Anatomical context of Cd244

• A newly generated monoclonal antibody (mAb C9.1) described in this study identifies a surface membrane molecule that is involved in the lytic programme of activated natural killer (NK) cells [11].
• However, the detection of mAb C9.1-reactive antigen on a minor subset of B cells may suggest a possible reactivity of mAb C9 [11].
• Cutting edge: Regulation of CD8(+) T cell proliferation by 2B4/CD48 interactions [14].
• Murine 2B4 (CD244) is a cell surface receptor expressed on all NK cells, gammadelta-T cells, a subset of CD8(+) T cells, and all CD14(+) monocytes [1].
• The expression of lymphoid cell surface markers on PBMC and splenocytes of mice homozygous for the mutation in 2B4 (2B4(-/-)) is identical to that in wild-type mice [1].

Associations of Cd244 with chemical compounds

• This localization of 2B4 occurs due to a CxC cysteine motif found in the transmembrane region, as determined by mutagenesis studies [15].
• They express on their surface the 2B4 molecule, a 66-kDa glycoprotein of the immunoglobulin gene superfamily thought to be associated with anti-tumor cytotoxicity by natural killer and lymphokine-activated killer cells [16].
• The cytoplasmic domain of 2B4 contains unique tyrosine motifs (TxYxxV/I) that associate with src homology 2 domain-containing protein or signaling lymphocyte activation molecule (SLAM)-associated protein, whose mutation is the underlying genetic defect in the X-linked lymphoproliferative disease (XLPD) [17].
• All five of these protease inhibitors enhanced rather than blocked 2B4 cell death triggered by dexamethasone, an agent previously shown to have a death pathway antagonistic with that of the TCR [18].
• 2B4 cytolysis by the cytotoxic agents staphylococcal alpha-toxin and dodecyl imidazole, and that caused by hypotonic conditions, was not significantly affected by the five protease inhibitors tested [18].

Physical interactions of Cd244

• NK cells from beta2 microglobulin (beta2m)-deficient mice and NK cells that lack expression of self-MHC-binding inhibitory receptors are inhibited by 2B4 [12].

Regulatory relationships of Cd244

• In contrast, the NK cell-activation receptors CD16 and 2B4 induced cytotoxicity but not IFN-gamma production [19].
• Furthermore, 2B4/CD48 interactions between NK cells also enhanced proliferation of NK cells in response to IL-2 [20].

Other interactions of Cd244

• Furthermore, the strain distribution of the C9.1 antigen was shown to be antithetical to that of the 2B4 antigen already described as a molecule associated with major histocompatibility complex-unrestricted killing mediated by activated NK cells [11].
• Furthermore, CHO killing did not correlate with expression of NK1.1 or 2B4 activation molecules [21].
• Previous studies have shown that treatment of NK cells with a 2B4 mAb results in increased cytotoxicity and IFN-gamma production [22].
• We show in this study that NK cells can enhance T cell activation and proliferation in response to CD3 cross-linking and specific Ag through interactions between 2B4 (CD244) on NK cells and CD48 on T cells [20].
• They are similar to NK cells and expressed NK cell receptors, including Ly49, CD94/NKG2, NKG2D, and 2B4 [23].

Analytical, diagnostic and therapeutic context of Cd244

• However, both populations are inhibited by 2B4 ligation [9].
• Northern blot analysis has shown at least three transcripts for 2B4 in adherent lymphokine-activated killer cells of several mouse strains and TCR-gamma/delta dendritic epidermal T cell lines but not in allospecific T cell clones [24].
• Southern blot analysis of genomic DNA from several mouse strains revealed that 2B4 belongs to a family of closely related genes [24].
• MAbs directed against CD2, CD48, or 2B4 were administered singly or in pairs to cardiac allograft recipients [25].
• Molecular cloning and characterization of the promoter region of murine natural killer cell receptor 2B4 [26].

References