Disease relevance of Klrb1c

• In the present report, a subset of cells coexpressing CD8 and NKR-P1C (NK1.1) was found in the lungs of mice infected with influenza A virus [1].
• To elucidate the role of NK1.1+ T cells in the antitumor immune response, we established cloned NK1.1+ T cell lines from tumor-infiltrating lymphocytes (TIL) of B16 melanoma, and examined their mode of action in generating antitumor effector T cells both in vitro and in vivo [2].
• Since NK-1.1 and NK-2.1 are also expressed on 2-3% of spleen cells of positive strains we suggest that all three alloantigens identify the NK cells in normal mouse spleen which lyse the lymphoma target cell line YAC [3].
• CD3- IL-2R beta- populations of both BM cells and hepatic MNC of C57BL/6 (B6) mice could generate T cells with intermediate TCR (mostly NK1.1-) in the liver of irradiated B6 SCID mice before thymic reconstitution (extrathymic T cells) [4].
• In addition, we show significant NK1.1 down-modulation on NKT cells in the setting of oral Salmonella infection [5].

Psychiatry related information on Klrb1c

• Alcohol consumption similarly reduced the percentages of NK1.1- and LGL-1-expressing lymphocytes in the peripheral blood and spleen and reduced the percentage of CD8+ T lymphocytes in the peripheral blood in both control and beige mice [6].

High impact information on Klrb1c

• One type of surface receptor such as the NKR-P1 molecule may activate NK activity whereas the other, represented by the mouse Ly-49 molecule, may engage target cell MHC molecules and inhibit cytotoxicity by transducing "negative" signals [7].
• The Ly-49 and NKR-P1 gene families encoding lectin-like receptors on natural killer cells: the NK gene complex [7].
• A lymphocyte subpopulation, the Valpha14 natural killer T (NKT) cells, expresses both NK1.1 and a single invariant T cell receptor encoded by the Valpha14 and Jalpha281 gene segments [8].
• CD1-deficient mice have normal numbers of CD4+ and CD8+ T cells but marked reduction in NK1.1-bearing T cells, particularly those with a canonical gene rearrangement of V alpha14-J alpha281 [9].
• Nkrp1 (official gene name, Klrb1) and Clr are intertwined in a genetically conserved NKC region showing recombination suppression, reminiscent of plant self-incompatibility loci [10].

Biological context of Klrb1c

• To investigate the NK1.1(-) phenotype of BALB/c NK cells, we have undertaken NK1.1 epitope mapping and genomic analysis of the BALB/c Nkrp1 region [11].
• Bacterial artificial chromosome library analysis reveals that, unlike the Ly49 region, the Nkrp1-Ocil/Clr region displays limited genetic divergence between B6 and BALB/c mice [11].
• Furthermore lack of NK1.1 expression on IL-2R beta+ T cells in SJL mice was found by backcross analysis to be controlled by a single recessive gene closely linked to the NKR-P1 complex on chromosome 6 (which encodes the NK1.1 antigen) [12].
• In contrast, defective TCR induced IL-4 production (which appeared to be a unique property of SJL mice) seems to be controlled by two recessive genes unlinked to NKR-P1 [12].
• Analysis of a panel of inbred mouse strains further demonstrated that lack of NK1.1 expression on IL-2R beta+ T cells segregated with NKR-P1 genotype (as assessed by restriction fragment length polymorphism) and thus was not restricted to the SJL strain [12].

Anatomical context of Klrb1c

• Molecular and genetic basis for strain-dependent NK1.1 alloreactivity of mouse NK cells [11].
• Natural killer-like T cells develop in SJL mice despite genetically distinct defects in NK1.1 expression and in inducible interleukin-4 production [12].
• Direct evidence for the presence of Fc gamma RII on murine NK cells is provided by the results of two-color immunofluorescence studies performed on splenic lymphocytes from C57BL/6 mice showing coexpression of NK-1.1 and 2.4G2 [13].
• Using these tetramers, we find that alpha-GalCer-specific T lymphocytes are more widely distributed than was previously appreciated, with populations of largely NK1.1(-) but tetramer-binding T cells present in the lymph nodes and the intestine [14].
• Mouse NKR-P1. A family of genes selectively coexpressed in adherent lymphokine-activated killer cells [15].

Associations of Klrb1c with chemical compounds

• Here, we demonstrate that both NKR-P1B and NKR-P1C associate with the tyrosine kinase, p56(lck) [16].
• Spleen virus titers were significantly augmented in B6 (NK1.1+) mice depleted of asialo GM1+ or NK1.1+ cells, whereas spleen virus titers were unaffected in D2 (NK1.1-) mice depleted of asialo GM1+ cells [17].
• We recently reported that IL-7 preferentially promotes the in vitro expansion of a discrete MHC class I-dependent lymphocyte subset comprising both CD4+ and CD4-CD8- TCR alpha beta + cells bearing several NK cells markers such NK1.1 and Ly-49 [18].
• With two other targets, E male G2 and RBL-5, neither serum produced significant depletion of activity, Analysis of SC indirectly labeled with either NK-1.1 or NK-2.1 antiserum and fluorescein-labeled goat anti-mouse Ig, however, did not detect significant differences between NK-1+ and NK-2+ cell populations [19].
• These findings demonstrate that the development of NK1.1+ TCR-alpha/beta+ thymocytes is accomplished under the influence not only of BM-derived components, but also of irradiation-resistant or deoxyguanosine-resistant components and an intact microenvironment of the thymus [20].

Regulatory relationships of Klrb1c

• Ly49C/I or Ly49A receptor was expressed on NK1.1+gamma/delta T cells but not on NK1.1-gamma/delta T cells [21].
• Second, most NK cells derived with IL-2 or IL-15 expressed the NK1.1 antigen, while those derived with IL-12 and IL-18 did not [22].
• TGF-beta could be an autocrine growth factor for NKL1.1+ T cells and thereby induce non-cytolytic NK1.1+ T cells in the long-term culture of TIL [23].
• Flt-3 ligand (FL) drives differentiation of rat bone marrow-derived dendritic cells expressing OX62 and/or CD161 (NKR-P1) [24].
• These colon NK1.1+ T cells activated by Lactobacilli were found to express IFN-gamma mRNA [25].

Other interactions of Klrb1c

• Mouse NKR-P1B, a novel NK1.1 antigen with inhibitory function [26].
• Strikingly, engagement of NKR-P1C on NK cells obtained from Lck-deficient mice failed to induce NK cytotoxicity [16].
• The mouse NKR-P1 family includes at least three genes: NKR-P1A, -B, -C [27].
• Collectively, our data indicate that "NK-like" T cells develop normally in SJL mice despite genetically distinct defects in NK1.1 expression and inducible IL-4 production [12].
• Allelic divergence of the Nkrp1b/c gene products and limited divergence of the BALB/c Nkrp1-Ocil/Clr region explain a longstanding confusion regarding the strain-specific NK1.1 alloantigen reactivity of mouse NK cells [11].

Analytical, diagnostic and therapeutic context of Klrb1c

• However, the BALB/c NKR-P1B/C sequences differ from those of the known NK1.1 alloantigens, and epitope mapping demonstrates that directed mutation of a single amino acid in the NKR-P1B(BALB) protein confers NK1.1 reactivity [11].
• By linkage analysis and pulsed field gel electrophoresis, a natural killer gene complex (NKC) on rat chromosome 4 is described that contains the rat NKR-P1 and Ly-49 multigene families plus a rat NKG2D homologue [28].
• The expression of the NKR-P1 genes in A-LAK cells from 13 mouse strains was examined by Northern blot analysis [29].
• Molecular cloning of the NK1.1 antigen, a member of the NKR-P1 family of natural killer cell activation molecules [30].
• We have isolated and expressed a member of the NKR-P1 gene family (mNKR-P1.9) and have demonstrated both by immunofluorescence and by immunoprecipitation that this cDNA encodes NK1 [30].

References