Identification of PVR (CD155) and Nectin-2 (CD112) as Cell Surface Ligands for the Human DNAM-1 (CD226) Activating Molecule
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- Cristina Bottino
- 1Istituto Giannina Gaslini, 16148 Genova, Italy
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- Roberta Castriconi
- 2Dipartimento di Medicina Sperimentale, Università di Genova, 16132 Genova, Italy
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- Daniela Pende
- 3Istituto Nazionale per la Ricerca sul Cancro, 16132 Genova, Italy
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- Paola Rivera
- 2Dipartimento di Medicina Sperimentale, Università di Genova, 16132 Genova, Italy
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- Marina Nanni
- 1Istituto Giannina Gaslini, 16148 Genova, Italy
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- Barbara Carnemolla
- 3Istituto Nazionale per la Ricerca sul Cancro, 16132 Genova, Italy
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- Claudia Cantoni
- 1Istituto Giannina Gaslini, 16148 Genova, Italy
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- Jessica Grassi
- 2Dipartimento di Medicina Sperimentale, Università di Genova, 16132 Genova, Italy
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- Stefania Marcenaro
- 1Istituto Giannina Gaslini, 16148 Genova, Italy
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- Nicolas Reymond
- 5Institut de Biologie du Cancer et d'Immunologie, INSERM U.119, 13009 Marseille, France
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- Massimo Vitale
- 3Istituto Nazionale per la Ricerca sul Cancro, 16132 Genova, Italy
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- Lorenzo Moretta
- 1Istituto Giannina Gaslini, 16148 Genova, Italy
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- Marc Lopez
- 5Institut de Biologie du Cancer et d'Immunologie, INSERM U.119, 13009 Marseille, France
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- Alessandro Moretta
- 2Dipartimento di Medicina Sperimentale, Università di Genova, 16132 Genova, Italy
抄録
<jats:p>Human natural killer (NK) cells express a series of activating receptors and coreceptors that are involved in recognition and killing of target cells. In this study, in an attempt to identify the cellular ligands for such triggering surface molecules, mice were immunized with NK-susceptible target cells. On the basis of a functional screening, four mAbs were selected that induced a partial down-regulation of the NK-mediated cytotoxicity against the immunizing target cells. As revealed by biochemical analysis, three of such mAbs recognized molecules of ∼70 kD. The other mAb reacted with two distinct molecules of ∼65 and 60 kD, respectively. Protein purification followed by tryptic digestion and mass spectra analysis, allowed the identification of the 70 kD and the 65/60 kD molecules as PVR (CD155) and Nectin-2 δ/α (CD112), respectively. PVR-Fc and Nectin-2-Fc soluble hybrid molecules brightly stained COS-7 cells transfected with the DNAM-1 (CD226) construct, thus providing direct evidence that both PVR and Nectin-2 represent specific ligands for the DNAM-1 triggering receptor. Finally, the surface expression of PVR or Nectin-2 in cell transfectants resulted in DNAM-1–dependent enhancement of NK-mediated lysis of these target cells. This lysis was inhibited or even virtually abrogated upon mAb-mediated masking of DNAM-1 (on NK cells) or PVR or Nectin-2 ligands (on cell transfectants).</jats:p>
収録刊行物
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- The Journal of Experimental Medicine
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The Journal of Experimental Medicine 198 (4), 557-567, 2003-08-11
Rockefeller University Press
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詳細情報 詳細情報について
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- CRID
- 1360574094447173120
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- NII論文ID
- 30017417199
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- ISSN
- 15409538
- 00221007
- http://id.crossref.org/issn/00221007
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- データソース種別
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- Crossref
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