Characterization of a novel gene (NKG7) on human chromosome 19 that is expressed in natural killer cells and T cells

Turman, Martin A.; Yabe, Toshikazu; McSherry, Cynthia; Bach, Fritz H.; Houchins, Jeffrey P.

doi:10.1016/0198-8859(93)90006-m

Cited by 61 publications

(40 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, as pulse-chase analysis did not support a precursor-product relationship between p40-TIA-1 and p15-TIA-1 (4), we purified p15-TIA-1 from the granules of a NK cell line (YT) and determined its N-terminal amino acid sequence. This sequence was found to be identical to the predicted N terminus of a cDNA-deduced structure previously isolated from NK cells and granulocyte-colony-stimulating factor (G-CSF)-treated mononuclear cells isolated from a patient with chronic myelogenous leukemia [designated NKG7 (6) and GIG-1 (7) 10 ,tg/ml and leupeptin at 50 ,ug/ml) and centrifuged at 100,000 x g for 30 min. The pellet was resuspended in lysis buffer containing 1% (vol/vol) Nonidet P-40 and centrifuged at 3000 x g for 10 min.…”

mentioning

confidence: 56%

“…GMP-17 (previously known as plS-TIA-1) is recognized by the 2G9 mAb, which has proven to be a useful reagent for the identification of cytotoxic lymphocytes infiltrating into sites of tissue destruction during graft-versus-host disease (18) and renal allograft rejection (19). Our results reveal that the primary structure of GMP-17 is encoded by cDNAs previously isolated by differential screening of NK cell and G-CSF-stimulated mononuclear cell cDNA libraries [clones NKG7 (6) and GIG-1 (7), respectively]. There is a strong correlation between the expression of GMP-17 and the expression of perforin and granzyme B in NK cells and CTLs (19,20), suggesting that GMP-17 may play a role in lymphocyte-mediated cytotoxicity.…”

Section: Resultsmentioning

confidence: 84%

See 1 more Smart Citation

Characterization of GMP-17, a granule membrane protein that moves to the plasma membrane of natural killer cells following target cell recognition.

Medley

Kedersha

O’Brien

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

104

View full text Add to dashboard Cite

Cytotoxic lymphocytes are characterized by their inclusion of cytoplasmic granules that fuse with the plasma membrane following target cell recognition. We previously identified a cytotoxic granule membrane protein designated p15-TIA-1 that is immunochemically related to an RNA-recognition motif (RRM)-type RNA-binding protein designated p40-TIA-1. Although it was suggested that p15-TIA-1 might be derived from p40-TIA-1 by proteolysis, N-terminal amino acid sequencing of p15-TIA-1 immunoaffinity purified from a natural killer (NK) cell line by using monoclonal antibody (mAb) 2G9 revealed that p15-TIA-1 is identical to the deduced amino acid sequence of NKG7 and GIG-1, cDNAs isolated from NK cells and granulocyte-colony-stimulating factor-treated mononuclear cells, respectively. Epitope mapping revealed that mAb 2G9 recognizes the C terminus of p15-TIA-1 and p40-TIA-1. The deduced amino acid sequence of p15-TIA-1/NKG7/GIG-1 predicts that the protein possesses four transmembrane domains, and immuno-electron microscopy localizes the endogenous protein to the membranes of cytotoxic granules in NK cells. Given its subcellular localization, we propose to rename this protein GMP-17, for granule membrane protein of 17 kDa. Immunofluorescence microscopy of freshly isolated NK cells confirms this granular localization. Target cell-induced NK cell degranulation results in translocation of GMP-17 from granules to the plasma membrane, suggesting a possible role for GMP-17 in regulating the effector function of lymphocytes and neutrophils.Natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) are characterized by their inclusion of cytoplasmic granules that are released in response to target cell recognition. Cytolytic lymphocyte granules are morphologically complex organelles that can either fuse with the plasma membrane, like secretory granules, or fuse with phagosomes, like primary lysosomes. Although cytotoxic granules are somewhat heterogeneous in structure, they typically contain one or more dense cores which are surrounded by multiple small internal vesicles (1, 2). The dense cores are the major reservoirs of secretory proteins such as perforin, granzymes, and chondroitin sulfate proteoglycans (1). In the multivesicular domain, which resembles endosomally derived multivesicular bodies found in many cell types, lysosomal membrane proteins such as lamp-1, lamp-2, and lgp-120 are abundantly expressed (1).At the C terminus of these proteins is a conserved motif that is required for their delivery to lysosome or granule membranes (3). We have characterized an 15-kDa granule membrane protein, designated p15-TIA-1, that is recognized by 2G9, a monoclonal antibody (mAb) that stains the granules ofThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.NK cells and CTLs (4, 5). Following lymphocyte activation, proteins migrating with apparent molecular masses of 28...

show abstract

mentioning

confidence: 56%

Section: Resultsmentioning

confidence: 84%

Characterization of GMP-17, a granule membrane protein that moves to the plasma membrane of natural killer cells following target cell recognition.

Medley

Kedersha

O’Brien

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

104

View full text Add to dashboard Cite

show abstract

“…Lower expression levels of inhibitory molecules CD94, NKG2A, and T cell exhaustion marker PD-1 (Figure 3 and 4), on the other hand, may suggest that T-bet −/− T cells can still preserve their cytotoxic function to overcome tumor growth, which was additionally supported by enhanced production of GZMB by T cells deficient for T-bet but not IFN-γ (Figure 4C). Nkg7 , a promoter of the T and NK cell surface cytotoxic molecule (55), has been considered as a Th1 cell-specific gene of which expression was previously shown to be regulated by T-bet (13, 56), and is positively correlated to cytotoxic T-cell destruction of epidermal cells in human GVHD (57). …”

Section: Discussionmentioning

confidence: 99%

T-bet Is Critical for the Development of Acute Graft-versus-Host Disease through Controlling T Cell Differentiation and Function

Wang

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

T-bet is a master regulator for IFN-γ production and Th1 differentiation. We evaluated the roles of T-bet and IFN-γ in T-cell responses in acute graft-versus-host disease (GVHD) and found that T-bet−/− T cells induced significantly less GVHD compared to WT or IFN-γ−/− counterparts in both MHC-mismatched and MHC-matched but minor histocompatibility antigen (miHA)-mismatched models driven by CD4 T cells. T-bet−/−, but not IFN-γ−/−, CD4 T cells had a markedly reduced ability to cause tissue damage in liver and gut. This distinct outcome is reflected by the differential gene expression on donor CD4 T cells deficient for T-bet or IFN-γ. At mRNA and protein levels, we defined several T-bet-dependent molecules that may account for the impaired ability of T-bet−/− T cells to migrate into target organs and to produce Th1-related cytokines. Moreover, these molecules were independent of either endogenous IFN-γ such as CXCR3 and PD-1, or systematic IFN-γ such as NKG2D, I-Ab, and granzyme B. Although both T-bet−/− and IFN-γ−/− CD4 T cells are prone to differentiate into Th17 cells, polarized Th17 cells deficient for T-bet but not for IFN-γ had a significantly reduced ability to cause GVHD. Finally, T-bet−/− T cells had compromised graft-versus-leukemia (GVL) effect, which could be essentially reversed by neutralization of IL-17 in the recipients. We conclude that T-bet is required for Th1 differentiation and migration, as well as for optimal function of Th17 cells. Thus, targeting T-bet or regulating its downstream effectors independent of IFN-γ may be a promising strategy to control GVHD in the clinic.

show abstract

“…14 -22 NKG7 is expressed on T cells, NK cells, and macrophages, and up-regulation has previously suggested an important role for the macrophage in renal allograft rejection. 23,24 Circulating TGF␤R3 binds to TGF␤ and facilitates its binding to TGF␤R1 and TGF␤R2 to mediate downstream signaling. 25 The functional significance of SYNE1 and GK5 has not been fully established in the immune response.…”

Section: Discussionmentioning

confidence: 99%

Increased Expression of Peripheral Blood Leukocyte Genes Implicate CD14+ Tissue Macrophages in Cellular Intestine Allograft Rejection

Ashokkumar

Ningappa

Ranganathan

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

Recurrent rejection shortens graft survival after intestinal transplantation (ITx) in children, most of whom also experience early acute cellular rejection (rejectors). To elucidate mechanisms common to early and recurrent rejection, we used a test cohort of 20 recipients to test the hypothesis that candidate peripheral blood leukocyte genes that trigger rejection episodes would be evident late after ITx during quiescent periods in genome-wide gene expression analysis and would achieve quantitative real-time PCR replication pre-ITx (another quiescent period) and in the early post-ITx period during first rejection episodes. Eight genes were significantly up-regulated among rejectors in the late post-ITx and pre-ITx periods, compared with nonrejectors: TBX21, CCL5, GNLY, SLAMF7, TGFBR3, NKG7, SYNE1, and GK5. Only

show abstract

Characterization of a novel gene (NKG7) on human chromosome 19 that is expressed in natural killer cells and T cells

Cited by 61 publications

References 27 publications

Characterization of GMP-17, a granule membrane protein that moves to the plasma membrane of natural killer cells following target cell recognition.

Characterization of GMP-17, a granule membrane protein that moves to the plasma membrane of natural killer cells following target cell recognition.

T-bet Is Critical for the Development of Acute Graft-versus-Host Disease through Controlling T Cell Differentiation and Function

Increased Expression of Peripheral Blood Leukocyte Genes Implicate CD14+ Tissue Macrophages in Cellular Intestine Allograft Rejection

Contact Info

Product

Resources

About