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J. Biol. Chem., Vol. 282, Issue 42, 30346-30356, October 19, 2007

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Polysialylated Neuropilin-2 Is Expressed on the Surface of Human Dendritic Cells and Modulates Dendritic Cell-T Lymphocyte Interactions^*

Sabrina Curreli, Zita Arany, Rita Gerardy-Schahn^¶1, Dean Mann, and Nicholas M. Stamatos^||2

From the Institute of Human Virology, University of Maryland, Baltimore, Maryland 21201, Department of Pathology and ^||Division of Infectious Diseases, Department of Medicine, University of Maryland Medical System, Baltimore, Maryland 21201, and ^¶Zentrum Biochemie, Abteilung Zellulare Chemie, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany

Polysialic acid (PSA) is a unique linear homopolymer of 2,8-linked sialic acid that has been identified as a posttranslational modification on only five mammalian proteins. Studied predominantly on neural cell adhesion molecule (NCAM) during development of the vertebrate nervous system, PSA modulates cell interactions mediated by NCAM and other adhesion molecules. An isoform of NCAM (CD56) on natural killer (NK) cells is the only protein known to be polysialylated in cells of the immune system, yet the function of PSA in NK cells remains unclear. We show here that neuropilin-2 (NRP-2), a receptor for the semaphorin and vascular endothelial growth factor families in neurons and endothelial cells, respectively, is expressed on the surface of human dendritic cells and is polysialylated. Expression of NRP-2 is up-regulated during dendritic cell maturation, coincident with increased expression of ST8Sia IV, one of the key enzymes of PSA biosynthesis, and with the appearance of PSA on the cell surface. PSA on NRP-2 is resistant to digestion with peptide N-glycosidase F but is sensitive to release under alkaline conditions, suggesting that PSA chains are added to O-linked glycans of NRP-2. Removal of polysialic acid from the surface of dendritic cells or binding of NRP-2 with specific IgG promoted dendritic cell-induced activation and proliferation of T lymphocytes. Thus, this newly recognized polysialylated protein on the surface of dendritic cells influences dendritic cell-T lymphocyte interactions through one or more of its distinct extracellular domains.

Received for publication, April 9, 2007 , and in revised form, July 24, 2007.

^* This work was supported in part by National Institutes of Health Grant K08 HL72176-03 (to N. M. S.) and by the generous support of Drs. Redfield and Gallo at the Institute of Human Virology. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Recipient of financial support from the Deutsche Forschungsgemeinschaft and the European Community (PROMEMORIA).

² To whom correspondence should be addressed: 725 West Lombard St., Institute of Human Virology, University of Maryland Medical System, Baltimore, MD 21201. Tel.: 410-706-2645; Fax: 410-706-4619; E-mail: stamatos{at}umbi.umd.edu.

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