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J. Biol. Chem., Vol. 280, Issue 23, 21955-21964, June 10, 2005

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Nectin-like Protein 2 Defines a Subset of T-cell Zone Dendritic Cells and Is a Ligand for Class-I-restricted T-cell-associated Molecule^*

Laurent Galibert, Geoffrey S. Diemer, Zhi Liu, Richard S. Johnson, Jeffrey L. Smith¶, Thierry Walzer¶||, Michael R. Comeau¶, Charles T. Rauch, Martin F. Wolfson, Rick A. Sorensen**, Anne-Renée Van der Vuurst de Vries**, Daniel G. Branstetter, Raymond M. Koelling, John Scholler**, William C. Fanslow**, Peter R. Baum¶, Jonathan M. Derry, and Wei Yan¶¶

From the Molecular Sciences, Protein Sciences, ^¶Inflammation, ^**Oncology, and Pathology, Amgen Inc., Seattle, Washington 98119-3105

Dendritic cells (DCs) are a phenotypically and functionally heterogenous population of leukocytes with distinct subsets serving a different set of specialized immune functions. Here we applied an in vitro whole cell panning approach using antibody phage display technology to identify cell-surface epitopes specifically expressed on human blood BDCA3⁺ DCs. A single-chain antibody fragment (anti-1F12 scFv) was isolated that recognizes a conserved surface antigen expressed on both human BDCA3⁺ DCs and mouse CD8⁺ DCs. We demonstrate that anti-1F12 scFv binds Nectin-like protein 2 (Necl2, Tslc1, SynCaM, SgIGSF, or Igsf4), an adhesion molecule involved in tumor suppression, synapse formation, and spermatogenesis. Thus, Necl2 defines a specialized subset of DCs in both mouse and human. We further show that Necl2 binds Class-I-restricted T-cell-associated molecule (CRTAM), a receptor primarily expressed on activated cytotoxic lymphocytes. When present on antigen presenting cells, Necl2 regulates IL-22 expression by activated CD8⁺ T-cells. We propose that Necl2/CRTAM molecular pair could regulate a large panel of cell/cell interactions both within and outside of the immune system.

Received for publication, February 23, 2005

^* 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.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. 1–3.

This article was selected as a Paper of the Week.

^|| Present address: Centre d'Immunologie de Marseille-Luminy, case906 13288 Marseille cedex 09, France.

Present address: Trubion Pharmaceuticals Inc, 2401 4th Ave., Suite 1050, Seattle, WA 98121.

^¶¶ To whom correspondence should be addressed: Amgen Inc., Molecular Sciences, AW2-D/3291, 1201 Amgen Ct., Seattle, WA 98119-3105. Tel.: 206-265-8045; Fax: 206-217-0346; E-mail: ywei{at}amgen.com.

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