Disease relevance of KLRB1

• Furthermore, the NKR-P1A(+) T cells in the human liver exhibited strong cytotoxicity against a variety of tumor cell lines including K562, Molt4 and some colonic adenocarcinoma cell lines [1].
• The lysis of melanoma cells by patient-derived CTLs was inhibited by the NK receptor CD94/NKG2A [2].
• All NK-cell lymphomas (4 nasal/oral and 1 intestinal) expressed at least 1 NKR, the CD94/NKG2A complex [3].
• CONCLUSION: The present study indicates that defective expression of NKR represents a novel mechanism contributing to impaired function of NK cells and CD8+ T cells in chronic hepatitis C [4].
• As the function of NK cells is primarily regulated by NK cell receptors (NKR), we analysed whether decreased NK cell function in hepatitis C may be related to dysregulated NKR expression [4].

High impact information on KLRB1

• This structure may serve as a prototype for other NK cell receptors such as Ly-49, NKR-P1, and CD69 [5].
• Two subsets of NK cells were identified in these cultures: one expressed both NKR-P1A and CD56 and, in variable proportions, all other NK cell differentiation antigens; the second subset expressed only NKR-P1A and, unlike the former, was not cytotoxic [6].
• This expression was paralleled by their ability to respond to both T cell receptor and NK receptor engagements [7].
• Urochordates and the origin of natural killer cells: identification of a CD94/NKR-P1-related receptor in blood cells of Botryllus [8].
• The formation of complexes between soluble, recombinant molecules indicates that HLA-Cw4 is sufficient for specific ligation by the NK receptor and that neither glycoprotein requires carbohydrate for the interaction [9].

Biological context of KLRB1

• Although rodent T cells only infrequently express NKR-P1, hNKR-P1A is present on approximately 25% of adult peripheral blood T cells, including both CD4+ and CD8+ T cells, and is expressed preferentially on adult T cells with a "memory" antigenic phenotype [10].
• Human (h)NKR-P1A cDNA was cloned from a NK cell cDNA library by expression in COS7 cells with the use of the DX1 mAb. hNKR-P1A is a type II membrane glycoprotein with characteristic properties of the C-type lectin superfamily [10].
• These data therefore define a novel signal transduction pathway for the CD161 (NKR-P1A) receptor and provide fresh insights into NK and NKT cell biology [11].
• NKR-P1A is on human chromosome 12, the syntenic of mouse chromosome 6, where the murine NKR-P1 genes are located [10].
• The IL-12-dependent NKRP1A up-regulation was abrogated by the incubation of NK cells with actinomycin D, thus suggesting that IL-12 induces de novo transcription of NKRP1A mRNA [12].

Anatomical context of KLRB1

• Human NK cells and subsets of T cells or NKT cells express the orphan C-type lectin receptor CD161 (NKR-P1A) of unknown function [13].
• One receptor whose function has remained largely enigmatic is human NKR-P1A (CD161), present on NK cells and subsets of T cells [14].
• CD161+ T cells were abundant in human intestinal epithelium as well as the liver [15].
• The jejunum showed the greatest abundance of CD161+ T cells among the intestinal regions investigated [15].
• This lymphocyte subset displays a slightly more limited T cell receptor V beta repertoire than the CD4+ NKRP1A- counterpart [16].

Associations of KLRB1 with chemical compounds

• Finally, mAb-mediated cross-linking of NKRP1A molecules in CD4+ T lymphocytes induced the up-regulation of the lymphocyte function-associated antigen 1 Mg(2+)-binding site as well as beta 1 and beta 2 integrin chains [16].
• Crosslinking of NKR-P1 on the cell surface induced transient in vivo tyrosine phosphorylation of cellular protein substrates [17].
• CHX treatment resulted also in an overexpression of AICL, LLT1, and CD161/NKR-P1A mRNAs [18].
• Exposure to the dihydropyridine drug nifedipine, which binds L-type calcium channels blocking calcium influx, prevents two dendritic cell functions that are dependent on extracellular calcium entry: apoptotic body engulfment and interleukin-12 production induced by cross-linking of the surface lectin NKRP1A [19].
• In conformity with the marked neuraminidase enhancement of NK-mediated cytolysis of the butyrate-induced targets, these NKR cells were associated with significantly enhanced levels of neuraminidase-accessible sialic acid compared to the NKS parental K562 cell line [20].

Physical interactions of KLRB1

• LLT1-containing liposomes bind to NKR-P1A+ cells, and binding is inhibited by anti-NKR-P1A mAb [14].

Regulatory relationships of KLRB1

• Moreover, LLT1 on target cells can inhibit NK cytotoxicity via interactions with NKR-P1A [14].
• Conversely, LLT1/CD161 interaction in the presence of a TCR signal enhanced IFN-gamma production by T cells [13].
• Almost all of the NKR-P1A(+) T cells in the human liver expressed CD69, suggesting that they were activated [1].
• Investigation of NK receptor expression showed that most CD56+ cells expressed membrane CD94 and NKG2-A mRNA [21].
• These data suggested that FK506 did not inhibit cytolytic activities of inhibitory NKR-expressing T cells and that there was a possibility of cytolytic activities being enhanced through the induction of cytotoxic molecules such as NKG2D and granzyme during a seven-day culture with FK506 [22].

Other interactions of KLRB1

• In this study, we demonstrate that the lectin-like transcript-1 (LLT1) is a physiologic ligand for NKR-P1A [14].
• CD161+ T (NT) cells exist predominantly in human intestinal epithelium as well as in liver [15].
• Engagement of CD161 on NK cells with LLT1 expressed on target cells inhibited NK cell-mediated cytotoxicity and IFN-gamma secretion [13].
• CD161 (human NKR-P1A) signaling in NK cells involves the activation of acid sphingomyelinase [11].
• Functional studies showed that the 191B8/NKRP1A molecule mediated strong inhibition of the cytolytic activity of cultured CD2- CD3- immature thymocytes against a panel of tumor target cells [23].

Analytical, diagnostic and therapeutic context of KLRB1

• Transfection of COS7 or NIH3T3 cells with hNKRP1A cDNA showed that the 191B8 mAb recognized NKRP1A as shown by both immunofluorescence analysis and immunoprecipitation experiments [23].
• We investigated the NKR distribution on NK and T cell subsets from uninfected and HIV-infected individuals, according to the clinical status, the absolute numbers of CD4+ T cells as well as the plasmatic viral load of the patients [24].
• Abnormal upregulation of the CD94/NKG2A inhibitory NKR on cytotoxic T cells (CTLs) could be responsible for a failure of immunosurveillance in cancer or HIV infection [25].
• The NKR-P1 and the CD94-containing complexes were independent of each other and both very large, as judged by Sepharose 4B gel chromatography [17].
• In the present study, we investigated the inhibitory natural killer cell receptor (NKR) expression of CD94/NKG2A on PBMC after allogeneic bone marrow transplantation (BMT) [26].

References