Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
X-linked lymphoproliferative disease: 2B4 molecules displaying inhibitory rather than activating function are responsible for the inability of natural killer cells to kill Epstein-Barr virus-infected cells
Autore:
Parolini, S; Bottino, C; Falco, M; Augugliaro, R; Giliani, S; Franceschini, R; Ochs, HD; Wolf, H; Bonnefoy, JY; Biassoni, R; Moretta, L; Notarangelo, LD; Moretta, A;
Indirizzi:
Univ Genoa, Dipartimento Med Sperimentale, Sez Istol, I-16132 Genoa, ItalyUniv Genoa Genoa Italy I-16132 imentale, Sez Istol, I-16132 Genoa, Italy Univ Brescia, Dipartimento Sci Biomed & Biotecnol, I-25123 Brescia, Italy Univ Brescia Brescia Italy I-25123 d & Biotecnol, I-25123 Brescia, Italy Ist Nazl Ric Canc, I-16132 Genoa, Italy Ist Nazl Ric Canc Genoa Italy I-16132 azl Ric Canc, I-16132 Genoa, Italy Univ Brescia, Pediat Clin, Ist Med Mol Angelo Nocivelli, I-25123 Brescia, Italy Univ Brescia Brescia Italy I-25123 elo Nocivelli, I-25123 Brescia, Italy Univ Washington, Dept Pediat, Seattle, WA 98195 USA Univ Washington Seattle WA USA 98195 , Dept Pediat, Seattle, WA 98195 USA Univ Vienna, Dept Immunol, A-1090 Vienna, Austria Univ Vienna Vienna Austria A-1090 , Dept Immunol, A-1090 Vienna, Austria Ctr Immunol Pierre Fabre, F-74164 St Julien En Genevois, France Ctr Immunol Pierre Fabre St Julien En Genevois France F-74164 is, France
Titolo Testata:
JOURNAL OF EXPERIMENTAL MEDICINE
fascicolo: 3, volume: 192, anno: 2000,
pagine: 337 - 346
SICI:
0022-1007(20000807)192:3<337:XLD2MD>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN NK CELLS; IMMUNOGLOBULIN SUPERFAMILY; SURFACE-MOLECULE; DOWN-REGULATION; ENCODING GENE; CUTTING EDGE; RECEPTOR; IDENTIFICATION; CYTOTOXICITY; LYMPHOCYTES;
Keywords:
X-linked lymphoproliferative disease; Epstein-Barr virus infection; natural killer cell; natural cytotoxicity receptor; 2B4 molecule;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Moretta, A Univ Genoa, Dipartimento Med Sperimentale, Sez Istol, Via GB Marsano 10, I-16132 Genoa, Italy Univ Genoa Via GB Marsano 10 Genoa Italy I-16132 Genoa, Italy
Citazione:
S. Parolini et al., "X-linked lymphoproliferative disease: 2B4 molecules displaying inhibitory rather than activating function are responsible for the inability of natural killer cells to kill Epstein-Barr virus-infected cells", J EXP MED, 192(3), 2000, pp. 337-346

Abstract

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 rum has been proposed to functionas 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 inhibitorysignals 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 NKcells, it did associate with Src homology 2 domain-containing phosphatase 1.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/09/20 alle ore 10:29:49