Oligosaccharide ligands for NKR-P1 protein activate NK cells and cytotoxicity

Bezouška, Karel; Yuen, Chun-Ting; O'brien, Jack J.; Childs, Robert A.; Chai, Wengang; Lawson, A. M.; Drbal, Karel; Fišerová, Anna; Pospísil, M; Feizi, Ten

doi:10.1038/372150a0

Cited by 248 publications

(137 citation statements)

References 45 publications

Supporting

Mentioning

133

Contrasting

Order By: Relevance

“…This is a recombinant protein prepared by bacterial expression of the extracellular portion of rat NKR-P1A antigen starting with leucine 66 [8]. It has been shown to be a carbohydrate binding protein (animal lectin [9]) that binds N-acetyl-D-glucosamine in its free or conjugated form [8,10,11] in addition to the spectrum of carbohydrates bearing acidic functionalities [12]. We have found that in plate inhibition experiments the low molecular mass GlcNAc-terminated glycoclusters are good ligands for sNKR-P1A with inhibition activities comparable with the classical high a¤nity neoglycoprotein ligands.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: GlcNAc‐terminated glycodendrimers form defined precipitates with the soluble dimeric receptor of rat natural killer cells, sNKR‐P1A

et al. 1998

Self Cite

View full text Add to dashboard Cite

Synthetic GlcNAc-terminated thiourea-bridged glycoclusters were found to be potent inhibitors of binding of the soluble dimeric receptor of rat natural killer cells, sNKR-P1A protein, to its high affinity ligand. Moreover, we have shown here that characteristic precipitation curves can be recorded upon mixing of the GlcNAc glycoclusters with sNKR-P1A. For the GlcNAc V glycocluster the precipitation curve is biphasic, with high affinity and low affinity precipitates differing in their sensitivity towards GlcNAc-mediated inhibition of precipitation. Quantitative analyses of the precipitates indicate the occurrence of a single sugar binding site per sNKR-P1A subunit, and lead to a model of the most possible spatial arrangements of the glycocluster-receptor lattices. These results provide new tools for further studies on carbohydrate recognition by NKR-P1A.z 1998 Federation of European Biochemical Societies.

show abstract

Section: Introductionmentioning

confidence: 99%

RETRACTED: GlcNAc‐terminated glycodendrimers form defined precipitates with the soluble dimeric receptor of rat natural killer cells, sNKR‐P1A

et al. 1998

Self Cite

View full text Add to dashboard Cite

show abstract

“…In support of this, we have previously shown that invariant Vα24+NKT-cells exhibit cytolytic antitumour activities against some tumour cell lines that do not express CD1d through killing mechanisms that are distinct from both those of NK-cells and T-cells (Nicol et al, 1999). Also, the presence of NKR-P1A receptors, which may be linked to the cytolytic activity, argues for an important cytotoxic function of human invariant Vα24+NKT-cells other than that exerted through TCR-mediated recognition of CD1d (Azzoni et al, 1998;Bezouska et al, 1994). Alternatively, the anti-tumour effects could be exerted through inhibition of proliferation, either by direct …”

mentioning

confidence: 99%

In vitro anti-tumour activity of α-galactosylceramide-stimulated human invariant Vα24+NKT cells against melanoma

et al. 2001

View full text Add to dashboard Cite

Summary α-galactosylceramide (KRN 7000, α-GalCer) has shown potent in vivo anti-tumour activity in mice, including against melanoma and the highly specific effect of inducing proliferation and activation of human Vα24+NKT-cells. We hypothesized that human Vα24+NKT-cells activated by α-GalCer might exhibit anti-tumour activity against human melanoma. To investigate this, Vα24+NKT-cells were generated from the peripheral blood of patients with melanoma after stimulation with α-GalCer pulsed monocyte-derived dendritic cells (Mo-DCs). Vα24+NKT-cells did not exhibit cytolytic activity against the primary autologous or allogeneic melanoma cell lines tested. However, proliferation of the melanoma cell lines was markedly suppressed by co-culture with activated Vα24+NKT-cells (mean ± SD inhibition of proliferation 63.9 ± 1.3%). Culture supernatants of activated Vα24+NKT-cell cultures stimulated with α-GalCer pulsed Mo-DCs exhibited similar antiproliferative activities against melanoma cells, indicating that the majority of the inhibitory effects were due to soluble mediators rather than direct cell-to-cell interactions. This effect was predominantly due to release of IFN-γ, and to a lesser extent IL-12. Other cytokines, including IL-4 and IL-10, were released but these cytokines had less antiproliferative effects. These in vitro results show that Vα24+NKT-cells stimulated by α-GalCer-pulsed Mo-DCs have anti-tumour activities against human melanoma through antiproliferative effects exerted by soluble mediators rather than cytolytic effects as observed against some other tumours. Induction of local cytokine release by activated Vα24+NKT-cells may contribute to clinical anti-tumour effects of α-GalCer.

show abstract

“…Among other NKRP1 family members, NKRP1A (with high sequence identity to NKRP1D and others in the NKRP1 family in the extracellular domain) has been reported to bind various sugars, including sulfated fucose-containing Le x and Le a oligosaccharides as well the HMW and LMW sugars that OCIL recognizes (8). The significance of OCIL recognition of similar sulfated sugars is unclear, but suggests that sugar recognition may play a role in the interaction of each of these molecules to enable NK cell mediated cytotoxicity, i.e.…”

Section: Discussionmentioning

confidence: 99%

“…Lectins are nonenzymatic sugar-binding proteins that bind specific carbohydrate moieties on cell surfaces, the extracellular matrix, and secreted glycoproteins, and such C-type lectin carbohydrate binding can play an important role in cellular functions (7,8). Alignment of the protein sequences of murine OCIL with human CD69 and rat mannose-binding protein A is shown in Fig.…”

mentioning

confidence: 99%

Characterization of Sugar Binding by Osteoclast Inhibitory Lectin

Gange

Quinn

Zhou

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

Osteoclast inhibitory lectin (OCIL) is a membranebound C-type lectin that blocks osteoclast differentiation and, via binding to its cognate receptor NKRP1D, inhibits natural killer cell-mediated cytotoxicity. OCIL is a member of the natural killer cell receptor C-type lectin group that includes CD69 and NKRP1D. We investigated carbohydrate binding of soluble recombinant human and mouse OCIL in enzyme-linked immunosorbent assay-based assays. OCIL bound immobilized high molecular weight sulfated glycosaminoglycans, including fucoidan, -carrageenan, and dextran sulfate, but not unsulfated dextran or sialated hyaluronic acid. Carbohydrate binding was Ca 2؉ -independent. Binding of immobilized low molecular weight glycosaminoglycans, including chondroitin sulfate (A, B, and C forms) and heparin, was not observed. However, the soluble forms of these low molecular weight glycosaminoglycans competed for OCIL binding of immobilized fucoidan (as did soluble fucoidan, dextran sulfate, and -carrageenan), indicating that OCIL does recognize these carbohydrates. Inhibition constants for chondroitin sulfate A and heparin binding were 380 and 5 nM, respectively. Immobilized and soluble monosaccharides did not bind OCIL. The presence of saturating levels of fucoidan, dextran sulfate, and -carrageenan did not affect OCIL inhibition of osteoclast formation. The fucoidan-binding lectins Ulex europaeus agglutinin I and Anguilla anguilla agglutinin did not block osteoclast formation or affect the inhibitory action of OCIL. Although the osteoclast inhibitory action of OCIL is independent of sugar recognition, we have found that OCIL, a lectin widely distributed, but notably localized in bone, skin, and other connective tissues, binds a range of physiologically important glycosaminoglycans, and this property may modulate OCIL actions upon other cells.

show abstract

Oligosaccharide ligands for NKR-P1 protein activate NK cells and cytotoxicity

Cited by 248 publications

References 45 publications

RETRACTED: GlcNAc‐terminated glycodendrimers form defined precipitates with the soluble dimeric receptor of rat natural killer cells, sNKR‐P1A

RETRACTED: GlcNAc‐terminated glycodendrimers form defined precipitates with the soluble dimeric receptor of rat natural killer cells, sNKR‐P1A

In vitro anti-tumour activity of α-galactosylceramide-stimulated human invariant Vα24+NKT cells against melanoma

Characterization of Sugar Binding by Osteoclast Inhibitory Lectin

Contact Info

Product

Resources

About