Molecular cloning and biological characterization of NK cell activation-inducing ligand, a counterstructure for CD48

Kubin, Marek; Parshley, Dorothy L.; Din, Wenie S.; Waugh, Jennifer Y.; Davis-Smith, Terri; Smith, Craig A.; Macduff, Brian M.; Armitage, Richard J.; Chin, Wilson; Cassiano, Linda; Borges, Luís; Petersen, Melissa A.; Trinchieri, Giorgio; Goodwin, Raymond G.

doi:10.1002/(sici)1521-4141(199911)29:11<3466::aid-immu3466>3.0.co;2-9

Cited by 81 publications

(60 citation statements)

References 40 publications

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“…Alternatively, only some cells may express sufficient surface densities of the ligand(s) to allow signaling upon binding with NTB-A. It is possible that NTB-A similar to CD150 42 may display homophilic interactions or interact with other members of the CD2 subfamily (as in the case of CD2/CD48, CD2/CD58, and 2B4/CD48 interactions) 21 22 43. Preliminary data would suggest that the ligand for NTB-A is not represented by CD48 (i.e., the 2B4 ligand).…”

Section: Discussionmentioning

confidence: 99%

“…2B4 is characterized, in its extracellular portion, by a membrane-distal IgV domain and a membrane-proximal IgC2 domain. The transmembrane region lacks charged amino acids involved in the association with immune tyrosine-based activating motif (ITAM)-bearing signal transducing polypeptides 21 22 25 26 27. Interestingly, the cytoplasmic tail contains four tyrosine-based motifs (TxYxxI/V) that undergo phosphorylation upon sodium pervanadate treatment 27 28 or cell triggering with anti-2B4 mAb 29.…”

Section: Introductionmentioning

confidence: 99%

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Gntb-A, a Novel Sh2d1a-Associated Surface Molecule Contributing to the Inability of Natural Killer Cells to Kill Epstein-Barr Virus–Infected B Cells in X-Linked Lymphoproliferative Disease

Bottino

Falco

Parolini

et al. 2001

The Journal of Experimental Medicine

290

343

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In humans, natural killer (NK) cell function is regulated by a series of receptors and coreceptors with either triggering or inhibitory activity. Here we describe a novel 60-kD glycoprotein, termed NTB-A, that is expressed by all human NK, T, and B lymphocytes. Monoclonal antibody (mAb)-mediated cross-linking of NTB-A results in the induction of NK-mediated cytotoxicity. Similar to 2B4 (CD244) functioning as a coreceptor in the NK cell activation, NTB-A also triggers cytolytic activity only in NK cells expressing high surface densities of natural cytotoxicity receptors. This suggests that also NTB-A may function as a coreceptor in the process of NK cell activation. Molecular cloning of the cDNA coding for NTB-A molecule revealed a novel member of the immunoglobulin superfamily belonging to the CD2 subfamily. NTB-A is characterized, in its extracellular portion, by a distal V-type and a proximal C2-type domain and by a cytoplasmic portion containing three tyrosine-based motifs. NTB-A undergoes tyrosine phosphorylation and associates with the Src homology 2 domain–containing protein (SH2D1A) as well as with SH2 domain–containing phosphatases (SHPs). Importantly, analysis of NK cells derived from patients with X-linked lymphoproliferative disease (XLP) showed that the lack of SH2D1A protein profoundly affects the function not only of 2B4 but also of NTB-A. Thus, in XLP-NK cells, NTB-A mediates inhibitory rather than activating signals. These inhibitory signals are induced by the interaction of NTB-A with still undefined ligands expressed on Epstein-Barr virus (EBV)-infected target cells. Moreover, mAb-mediated masking of NTB-A can partially revert this inhibitory effect while a maximal recovery of target cell lysis can be obtained when both 2B4 and NTB-A are simultaneously masked. Thus, the altered function of NTB-A appears to play an important role in the inability of XLP-NK cells to kill EBV-infected target cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Gntb-A, a Novel Sh2d1a-Associated Surface Molecule Contributing to the Inability of Natural Killer Cells to Kill Epstein-Barr Virus–Infected B Cells in X-Linked Lymphoproliferative Disease

Bottino

Falco

Parolini

et al. 2001

The Journal of Experimental Medicine

290

343

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“…3a), and its expression remained unchanged during the whole NK cell differentiation process. The 2B4 ligand, represented by CD48 (28), was expressed at low density in fresh CD34 ϩ cells but, upon culture, was up-regulated in all differentiating cells, including both immature NK cells and bystander myelomonocytic cell precursors (Fig. 3a).…”

Section: Early Expression Of Triggering Nk Receptors By Immature Nk Cmentioning

confidence: 99%

Early expression of triggering receptors and regulatory role of 2B4 in human natural killer cell precursors undergoingin vitrodifferentiation

Sivori

Falco

Marcenaro

et al. 2002

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

179

172

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In this study we analyzed the progression of cell surface receptor expression during the in vitro-induced human natural killer (NK) cell maturation from CD34 ؉ Lin ؊ cell precursors. NKp46 and NKp30, two major triggering receptors that play a central role in natural cytotoxicity, were expressed before the HLA class I-specific inhibitory receptors. Moreover, their appearance at the cell surface correlated with the acquisition of cytolytic activity by developing NK cells. Although the early expression of triggering receptors may provide activating signals required for inducing further cell differentiation, it may also affect the self-tolerance of developing NK cells. Our data show that a fail-safe mechanism preventing killing of normal autologous cells may be provided by the 2B4 surface molecule, which, at early stages of NK cell differentiation, functions as an inhibitory rather than as an activating receptor.

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“…Alternatively, individual cell types from human peripheral blood were isolated from multiple donors, and stimulations were performed as described (33,34,41). In brief, NK cells were incubated with IL-12 (R & D Biosystems; 1 ng/ml) for either 2 or 4 h. T cells were unstimulated or stimulated with anti-CD3 (OKT-3 antibody, immobilized on plastic at 5 g/ml) or with the combination of anti-CD3 and anti-CD28 (the anti-CD28 antibody was CK248, used in soluble form as a 1:500 dilution of ascites fluid), for 4 h. Monocytes were unstimulated, or stimulated with LPS (Sigma, 1 g/ml) for 2 or 3 h. B cells were unstimulated, or stimulated with a combination of 005% SAC ϩ 500 ng/ml CD40L trimer (Immunex) ϩ 5 ng/ml IL-4 (Immunex) for 3.5 or 4 h. Dendritic cells were stimulated with LPS as for monocytes for 2 or 4 h. After isolation of RNA and synthesis of first-strand cDNA, PCR amplifications and gel analysis were performed as described above.…”

Section: Expression Analysismentioning

confidence: 99%

Four New Members Expand the Interleukin-1 Superfamily

Smith

Renshaw

Ketchem

et al. 2000

Journal of Biological Chemistry

305

232

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We report here the cloning and characterization of four new members of the interleukin-1 (IL-1) family (FIL1␦, FIL1⑀, FIL1, and FIL1, with FIL1 standing for "Family of IL-1"). The novel genes demonstrate significant sequence similarity to IL-1␣, IL-1␤, IL-1ra, and IL-18, and in addition maintain a conserved exon-intron arrangement that is shared with the previously known members of the family. Protein structure modeling also suggests that the FIL1 genes are related to IL-1␤ and IL-1ra. The novel genes form a cluster with the IL-1s on the long arm of human chromosome 2.The cytokine interleukin-1 (IL-1) 1 elicits a wide array of biological activities that initiate and promote the host response to injury or infection, including fever, sleep, loss of appetite, acute phase protein synthesis, chemokine production, adhesion molecule up-regulation, vasodilatation, the pro-coagulant state, increased hematopoiesis, and production and release of matrix metalloproteinases and growth factors (1). It does so by activating a set of transcription factors that includes NFB and AP-1, which in turn promote production of effectors of the inflammatory response, such as the inducible forms of cycloxygenase and nitric oxide synthase (2, 3). Interleukin 1 activity actually resides in each of two molecules, IL-1␣ and IL-1␤, which act by binding to a common receptor composed of a ligand binding chain, the type I IL-1 receptor, and a required signaling component, the IL-1R accessory protein (AcP) (4 -7). A third member of the family, the IL-1 receptor antagonist (IL-1ra), also binds to the type I IL-1 receptor but fails to bring about the subsequent interaction with AcP, thus not only not signaling itself but also, by blocking the receptor, preventing the action of the agonist IL-1s (8, 9). Additional regulation is provided by the type II, or decoy, IL-1 receptor, which binds and sequesters the agonist IL-1s (especially IL-1␤) without inducing any signaling response of its own (10 -13). The two agonist IL-1s (IL-1␣ and IL-1␤) are synthesized as larger precursors which undergo proteolytic removal of their pro-domains to generate the mature cytokines (14). At least for IL-1␤, this processing is coupled to secretion (15, 16). IL-1ra, in contrast, contains a signal peptide and is secreted by the more traditional route through the endoplasmic reticulum (9).Recently, another cytokine, interleukin 18 (17, 18) was recognized to be related to the interleukin-1 family based on the similarity of its amino acid sequence and predicted tertiary structure (19). IL-18 induces the production of ␥-interferon from T cells, especially in combination with IL-12, and stimulates the killing activity of cytotoxic T lymphocytes and NK cells by . Like the agonist IL-1s, IL-18 contains a prodomain that is removed by the same protease, caspase-1, that processes IL-1␤ (21, 22). Consistent with its being related to the IL-1s, IL-18 binds a receptor which is homologous to the IL-1 receptor. The ligand-binding chain IL1Rrp1 (or IL-18R␣) (23, 24) was cloned initially on ...

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Molecular cloning and biological characterization of NK cell activation-inducing ligand, a counterstructure for CD48

Cited by 81 publications

References 40 publications

Gntb-A, a Novel Sh2d1a-Associated Surface Molecule Contributing to the Inability of Natural Killer Cells to Kill Epstein-Barr Virus–Infected B Cells in X-Linked Lymphoproliferative Disease

Gntb-A, a Novel Sh2d1a-Associated Surface Molecule Contributing to the Inability of Natural Killer Cells to Kill Epstein-Barr Virus–Infected B Cells in X-Linked Lymphoproliferative Disease

Early expression of triggering receptors and regulatory role of 2B4 in human natural killer cell precursors undergoingin vitrodifferentiation

Four New Members Expand the Interleukin-1 Superfamily

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