Disease relevance of Klrb1@

• We also compared the lytic capacity of NKR-P1+ populations derived from normal animals and from 9L gliosarcomas [1].

High impact information on Klrb1@

• Oligosaccharide ligands for NKR-P1 protein activate NK cells and cytotoxicity [2].
• Interactions of such oligosaccharides on the target cell surface with NKR-P1 on the killer cell surface are crucial both for target cell recognition and for delivery of stimulatory or inhibitory signals linked to the NK cytolytic machinery [2].
• Rat spleen dendritic cells express natural killer cell receptor protein 1 (NKR-P1) and have cytotoxic activity to select targets via a Ca2+-dependent mechanism [3].
• By one-parameter flow cytometry, it was determined that NKR-P1+ cells constituted 30-60% of the lymphocytes in 9L tumors [1].
• Previous investigations have determined the existence of three populations of NKR-P1+ lymphocytes in normal rats, including NKR-P1bright/T-cell receptor (TCR)-/CD3-/CD5- (approximately 5-15%), NKR-P1dim-/TCRalphabeta+/CD3+/CD5+ (approximately 1-5%), and NKR-P1dim/TCRgammadelta+/CD3+/CD5+ (approximately 0.5-2%) [1].

Biological context of Klrb1@

• NKR-P1, a signal transduction molecule on natural killer cells [4].
• Cells of this phenotype have not been reported previously, and most likely represent NK cells down-modulated for expression of NKR-P1 [1].
• These data indicate that NKR-P1bright/L.E.bright and NKR-P1bright/L.E.dim subpopulations of rat NK cells have different capacities for: 1) triggering through NKR-P1; and 2) E-A rosette formation and lysis of antibody-sensitized target cells by ADCC [5].
• Dimerization of soluble NKR-P1 is predominantly dependent on the presence of an intact juxta-membrane stalk region and independent of N-glycosylation [6].
• However, spontaneous functions of liver-resident NK cells, including killing of YAC-1 and P815 targets, Ab-dependent cellular cytotoxicity, and redirected killing via NKR-P1, were continuously suppressed throughout the entire period of liver regeneration (from 3 h to 14 days) [7].

Anatomical context of Klrb1@

• We have expressed a full-length NKR-P1 protein of the rat in COS cells and prepared soluble extracellular fragments by controlled proteolysis or by expression of truncated cDNA in bacteria [6].
• We previously reported that the 70-kDa heat shock cognate protein-like molecule (hsc70) is expressed on the cell surface along with the neoplastic transformation of rat fibroblast and that this molecule is recognized by CD3+, CD4-, CD8-, NKR-P1-, and TCR-alphabeta- T (DNT) killer cells in an MHC class I-unrestricted fashion [8].
• Immunoprecipitation studies showed that p56(lck) can be co-immunoprecipitated with NKR-P1 from a rat NK tumor cell line [9].
• Flow cytometry analysis before and at disease onset revealed a higher proportion of lymph node T cells expressing NKR-P1 in the disease-resistant LEW.1AV1 compared with the disease-susceptible DA strain, suggesting that NK T cells might be disease protective [10].
• In graft recipients it was evident that activated monocytes were able to express and upregulate NKR-P1 and CD8, which have not been detected in these cells to date [11].

Associations of Klrb1@ with chemical compounds

• We here demonstrate that F(ab')2 antibody to NKR-P1 stimulates phosphoinositide turnover and a rise in intracellular calcium within RNK-16 cells [12].
• The CD45-negative cells expressed CD2, CD53, and NKR-P1, but mAb-induced perturbations of these molecules did not induce protein tyrosine phosphorylations and increases in the concentration of cytoplasmic-free calcium, as occurred in the wild-type RNK-16 [13].
• Binding and inhibition studies using monosaccharides and neoglycoconjugates indicate that NKR-P1 is a lectin with a preference order of GalNAc > GlcNAc >> Fuc >> Gal > Man. At neutral pH, Ca2+ is tightly associated with the protein such that only a proportion can be removed by 10 mM EGTA [6].
• Thy cytoplamic domain of rat NKR-P1 receptor interacts with the N-terminal domain of p56(lck) via cysteine residues [14].
• NKR-P1 triggering, which is known to induce NK cell activation and mediate reverse ADCC, was able to induce arginine metabolism with consequent increase of nitrite and citrulline levels [15].

Other interactions of Klrb1@

• In contrast, this protection was not abolished by the addition of anti-rat IL-2 or anti-rat TNF-alpha, or by the depletion of NKR-P1-bearing cells within gammadelta T cells [16].
• NKR-P1 molecules constitute a family of type II membrane receptors in natural killer (NK) cells that preferentially activate NK cell killing and release of interferon-gamma from these cells [17].
• Functional coupling of NKR-P1 receptors to various heterotrimeric G proteins in rat interleukin-2-activated natural killer cells [17].
• In addition, the NK subpopulation exhibiting the allocytolytic activity in alloimmunized rats exhibited a decreased expression of the NKR-P1 and L-selectin molecules, but an increased expression of the LFA-1 molecule when compared to NK cells from naive rats [18].

Analytical, diagnostic and therapeutic context of Klrb1@

• Phenotype of rat monocytes during acute kidney allograft rejection: increased expression of NKR-P1 and reduction of CD43 [11].

References