Results

RDF/XMLNTriplesTurtleShow queryShare ▶
SubjectPredicateObject
http://purl.uniprot.org/citations/10934222http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/10934222http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/10934222http://www.w3.org/2000/01/rdf-schema#comment"2B4 is a surface molecule involved in activation of the natural killer (NK) cell-mediated cytotoxicity. It binds a protein termed Src homology 2 domain-containing protein (SH2D1A) or signaling lymphocyte activation molecule (SLAM)-associated protein (SAP), which in turn has been proposed to function as a regulator of the 2B4-associated signal transduction pathway. In this study, we analyzed patients with X-linked lymphoproliferative disease (XLP), a severe inherited immunodeficiency characterized by critical mutations in the SH2D1A gene and by the inability to control Epstein-Barr virus (EBV) infections. We show that, in these patients, 2B4 not only fails to transduce triggering signals, but also mediates a sharp inhibition of the NK-mediated cytolysis. Other receptors involved in NK cell triggering, including CD16, NKp46, NKp44, and NKp30, displayed a normal functional capability. However, their activating function was inhibited upon engagement of 2B4 molecules. CD48, the natural ligand of 2B4, is highly expressed on the surface of EBV(+) B cell lines. Remarkably, NK cells from XLP patients could not kill EBV(+) B cell lines. This failure was found to be the consequence of inhibitory signals generated by the interaction between 2B4 and CD48, as the antibody-mediated disruption of the 2B4-CD48 interaction restored lysis of EBV(+) target cells lacking human histocompatibility leukocyte antigen (HLA) class I molecules. In the case of autologous or allogeneic (HLA class I(+)) EBV(+) lymphoblastoid cell lines, restoration of lysis was achieved only by the simultaneous disruption of 2B4-CD48 and NK receptor-HLA class I interactions. Molecular analysis revealed that 2B4 molecules isolated from either XLP or normal NK cells were identical. As expected, in XLP-NK cells, 2B4 did not associate with SH2D1A, whereas similar to 2B4 molecules isolated from normal NK cells, it did associate with Src homology 2 domain-containing phosphatase 1."xsd:string
http://purl.uniprot.org/citations/10934222http://purl.org/dc/terms/identifier"doi:10.1084/jem.192.3.337"xsd:string
http://purl.uniprot.org/citations/10934222http://purl.org/dc/terms/identifier"doi:10.1084/jem.192.3.337"xsd:string
http://purl.uniprot.org/citations/10934222http://purl.uniprot.org/core/author"Wolf H."xsd:string
http://purl.uniprot.org/citations/10934222http://purl.uniprot.org/core/author"Wolf H."xsd:string
http://purl.uniprot.org/citations/10934222http://purl.uniprot.org/core/author"Notarangelo L.D."xsd:string
http://purl.uniprot.org/citations/10934222http://purl.uniprot.org/core/author"Notarangelo L.D."xsd:string
http://purl.uniprot.org/citations/10934222http://purl.uniprot.org/core/author"Bottino C."xsd:string
http://purl.uniprot.org/citations/10934222http://purl.uniprot.org/core/author"Bottino C."xsd:string
http://purl.uniprot.org/citations/10934222http://purl.uniprot.org/core/author"Ochs H.D."xsd:string
http://purl.uniprot.org/citations/10934222http://purl.uniprot.org/core/author"Ochs H.D."xsd:string
http://purl.uniprot.org/citations/10934222http://purl.uniprot.org/core/author"Falco M."xsd:string
http://purl.uniprot.org/citations/10934222http://purl.uniprot.org/core/author"Falco M."xsd:string
http://purl.uniprot.org/citations/10934222http://purl.uniprot.org/core/author"Moretta L."xsd:string
http://purl.uniprot.org/citations/10934222http://purl.uniprot.org/core/author"Moretta L."xsd:string
http://purl.uniprot.org/citations/10934222http://purl.uniprot.org/core/author"Parolini S."xsd:string
http://purl.uniprot.org/citations/10934222http://purl.uniprot.org/core/author"Parolini S."xsd:string
http://purl.uniprot.org/citations/10934222http://purl.uniprot.org/core/author"Bonnefoy J.-Y."xsd:string
http://purl.uniprot.org/citations/10934222http://purl.uniprot.org/core/author"Bonnefoy J.-Y."xsd:string
http://purl.uniprot.org/citations/10934222http://purl.uniprot.org/core/author"Augugliaro R."xsd:string
http://purl.uniprot.org/citations/10934222http://purl.uniprot.org/core/author"Augugliaro R."xsd:string
http://purl.uniprot.org/citations/10934222http://purl.uniprot.org/core/author"Biassoni R."xsd:string
http://purl.uniprot.org/citations/10934222http://purl.uniprot.org/core/author"Biassoni R."xsd:string
▶