Disease relevance of KIR2DL3

• Similarly, interactions of KIR2DL2 or KIR2DL3 (KIR2DL2/3) with HLA-Cw3-related allotypes on melanomas resulted in decreased tumor cell lysis [1].
• The extracellular region of a p58 KIR specific for HLA-Cw1,3,7 (KIR2) has been overproduced in Escherichia coli and purified [2].
• TCR gamma delta cytotoxic T lymphocytes expressing the killer cell-inhibitory receptor p58.2 (CD158b) selectively lyse acute myeloid leukemia cells [3].
• RESULTS: There was a decreased expression of NKB1 and GL183 on NK cells in the endometrium, but not in the myometrium, in women with adenomyosis [4].
• Killer inhibitory receptor (CD158b) modulates the lytic activity of tumor-specific T lymphocytes infiltrating renal cell carcinomas [5].

Psychiatry related information on KIR2DL3

• When the reaction time of alpha-amylase was 30 min, the limit of detection was 0.5 nkat ml(-1) [6].
• In the group with bipolar disorder, treated with lithium (7.39 nkat/l+/-3.11) and, in the group of patients treated with psychiatric drugs because of various mental disorders (7.79 nkat/l+/-8.51), the differences are statistically significant [7].

High impact information on KIR2DL3

• The human p58 natural killer-cell inhibitory receptor clone 42 recognizes HLA-Cw4, -Cw2 and -Cw6, but not HLA-Cw3, -Cw2, -Cw7 or -Cw8, which are recognized by p58 killer-cell inhibitor receptor clone 43 [8].
• We have determined the X-ray structure of the p58 NK-cell inhibitory receptor clone 42 at 1.7-A resolution [8].
• Using mice that are transgenic for KIR2DL3 and its cognate HLA-Cw3 ligand, we show that engagement of inhibitory NKRs selectively drives the in vivo accumulation of a subset of memory-phenotype CD8+ T cells that express the beta chain of the interleukin 2 receptor [9].
• Furthermore, the cytoplasmic domain of Ly-49D does not contain the V/Ix-YxxL immunoreceptor tyrosine-based inhibitory motif found in Ly-49A, C, or G2 that has been characterized in the human p58 killer inhibitory receptors [10].
• The natural killer (NK) cell-specific p58 molecules EB6 and GL183 have been shown to represent the putative surface receptors for two distinct groups of human histocompatibility leukocyte antigen (HLA) C alleles [11].

Chemical compound and disease context of KIR2DL3

• Infected cells were labeled with chromium-51, treated with a cocktail of four different monoclonal antibodies against HIV gp120, and co-cultured with freshly isolated autologous NK cells that were incubated with or without anti-CD159a, anti-CD158a, and CD158b, or all three antibodies combined [12].
• The new biosensor has the limit of detection of 50 nmol l(-1) maltose, which means 2 nkat ml(-1) in alpha-amylase activity units, when the reaction time of amylase was 5 min (determined with respect to a signal-to-noise ratio 3:1) [6].
• L-Serine dehydratase with a specific activity of 15 nkat/mg protein was present in the anaerobic eubacterium Peptostreptococcus asaccharolyticus grown either on L-glutamate or L-serine [13].
• The ORM1 phenotype showed a significant increase in sarcoidosis (RR = 1.34, p = 0.036), which was more pronounced among patients with low (< 1,500 nkat/l) angiotensin-converting enzyme levels (RR = 1.83, p = 0.00065) and hypercalcemia (RR = 3.69, p = 0.0023) [14].
• Using [35S] methionine-labeled cell lines and immunoprecipitation, we have demonstrated the constitutive expression of p70 as well as a major component at p58 and a number at lower molecular weights in the myeloid leukemia cell lines HL60, KG1, K562 and U937, but not in the lymphocytic leukemia cell lines Molt-4, Hut-78 and CEM [15].

Biological context of KIR2DL3

• In contrast, we show that KIR2DL3 binds RYRPGTVAL/HLA-Cw7 with fast kinetics and a favorable binding entropy, consistent with rigid body association [16].
• We show here that the frequency of CD16+CD158b+, but not CD16-CD158b+ NK cells, was significantly lower (p <0.026) in homozygotes for HLA-Cw7 (NKI ligand) haplotypes than in heterozygotes [17].
• p58 Killer cell inhibitory receptors (KIRs) recognize HLA-C molecules on target cell surface and transmit an inhibitory signal to prevent cell-mediated cytotoxicity. p58 KIR family is composed of multiple receptors whose amino acid sequences are similar but their ligand specificity is different [18].
• Putative splicing sites found in p58 KIR cDNAs suggest that the differently spliced forms are produced by alternative splicing mechanism, and that the hybrid KIRs may also be generated by alternative splicing of two consecutive genes and/or by trans-splicing mechanism found in Ig genes in B cells [18].
• The direct binding of a p58 killer cell inhibitory receptor to human histocompatibility leukocyte antigen (HLA)-Cw4 exhibits peptide selectivity [19].

Anatomical context of KIR2DL3

• Modulation of T-cell functions in KIR2DL3 (CD158b) transgenic mice [20].
• In contrast, antigen and anti-CD3 MoAb-induced cytotoxicity exerted by alloreactive cytotoxic T lymphocytes cannot be inhibited by KIR2DL3 engagement [20].
• In contrast, one or both allelic forms of KIR2DL2/KIR2DL3 were expressed by a high proportion of NK cells in all 73 individuals [21].
• Investigation of killer cell immunoglobulin-like receptor gene diversity III. KIR2DL3 [22].
• To investigate the interaction between p58 NK receptors and HLA-Cw4, the extracellular domain of the p58 NK receptor specific for HLA-Cw4 was overexpressed in Escherichia coli and refolded from purified inclusion bodies [23].

Associations of KIR2DL3 with chemical compounds

• Two of these polypeptides can be identified as nuclear lamins A and B. The immunoisolate also contains a kinase activity that phosphorylates p58 in vivo and in vitro, exclusively at serine residues, as indicated by phosphoamino acid analysis and two-dimensional phosphopeptide mapping [24].
• Binding of p58 to T3 and its analogs resulted in the inhibition of its pyruvate kinase activity [25].
• Conversion of p58 to the tetramer is reversible and is under the control of fructose 1,6-bisphosphate [25].
• This p58 protein was purified from the WERI-1 cell nuclear extract by ammonium sulfate precipitation, Mono Q chromatography, and immunoprecipitation with anti-Sm antibody Y12 [26].
• Its isoelectric point was determined to be 7.1, which is different from the reported pIs of other thyroid hormone binding proteins. p58 was successively purified to apparent homogeneity by chromatography on Sephadex G-200, QAE-Sephadex, SP-Sephadex, and hydroxylapatite [27].

Regulatory relationships of KIR2DL3

• First, we show using plastic-immobilized CD158b mAb that the activating KIR2DS2 is stimulated, resulting in NK cell division and degranulation [28].

Other interactions of KIR2DL3

• Here we use surface plasmon resonance to study the binding of soluble forms of KIR2DL1 and KIR2DL3 to several peptide-HLA-Cw7 complexes [16].
• We have generated transgenic mice expressing an IgSF KIR, CD158b (p58.2), which recognizes HLA-Cw3 [29].
• Patients with advanced disease (Binet stage C) had a significantly greater percentage of CTL expressing CD158b, CD158e and CD94 than patients with non-progressive disease (Binet stage A) and healthy controls [30].
• We also find that CD158b inhibitory receptors partially interfere with CD160-mediated cytotoxicity, whereas CD94CD159a and CD85j have no effect on engagement with their respective ligands [31].
• Expression of HLA-C-specific natural killer cell receptors (CD158a and CD158b) on peripheral blood mononuclear cells after allogeneic bone marrow transplantation [32].

Analytical, diagnostic and therapeutic context of KIR2DL3

• As expected, mixed lymphocyte reaction and anti-CD3 monoclonal antibody (MoAb)-redirected cytotoxicity exerted by freshly isolated splenocytes can be inhibited by engagement of transgenic KIR2DL3 molecules [20].
• Molecular cloning of the p58 NK receptor reported here revealed a new member of the immunoglobulin superfamily [33].
• Crystallization and preliminary diffraction studies of the extracellular region of human p58 killer cell inhibitory receptor (KIR2) [2].
• Double immunofluorescence staining with A803g and anti-CD56 Ab showed that CD56 and p58 or p50 were expressed on NK cells in a mutually exclusive way [34].
• MAIN OUTCOME MEASURE(S): NK cytotoxicity was determined by assay of (51)Cr release against K562 cells, and the expression of killer cell inhibitory receptors (KIR, including NKB1, GL183, and EB6) in NK cells was examined by flow cytometry [35].

References