HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 31, 22370-22375, August 3, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/31/22370    most recent M704250200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Hoffmann, S. C. Articles by Watzl, C. Search for Related Content PubMed PubMed Citation Articles by Hoffmann, S. C. Articles by Watzl, C. Social Bookmarking                      What's this?

Identification of CLEC12B, an Inhibitory Receptor on Myeloid Cells^*

Sabrina C. Hoffmann¹, Carola Schellack², Sonja Textor, Stephanie Konold^¶, Debora Schmitz^¶, Adelheid Cerwenka², Stefan Pflanz^¶, and Carsten Watzl¹³

From the Institute for Immunology, University of Heidelberg, Im Neuenheimer Feld 305, 69120 Heidelberg, Division of Innate Immunity, German Cancer Research Center/D080, Im Neuenheimer Feld 280, 69120 Heidelberg and ^¶Micromet AG, Staffelseestrasse 2, 81477 München, Germany

Activation of immune cells has to be tightly controlled to prevent detrimental hyperactivation. In this regulatory process molecules of the C-type lectin-like family play a central role. Here we describe a new member of this family, CLEC12B. The extracellular domain of CLEC12B shows considerable homology to the activating natural killer cell receptor NKG2D, but unlike NKG2D, CLEC12B contains an immunoreceptor tyrosine-based inhibition motif in its intracellular domain. Despite the homology, CLEC12B does not appear to bind NKG2D ligands and therefore does not represent the inhibitory counterpart of NKG2D. However, CLEC12B has the ability to counteract NKG2D-mediated signaling, and we show that this function is dependent on the immunoreceptor tyrosine-based inhibition motif and the recruitment of the phosphatases SHP-1 and SHP-2. Using monoclonal anti-CLEC12B antibodies we found de novo expression of this receptor on in vitro generated human macrophages and on the human myelo-monocytic cell line U937 upon phorbol 12-myristate 13-acetate treatment, suggesting that this receptor plays a role in myeloid cell function.

Received for publication, May 23, 2007

^* 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 Supported by the Deutsche Forschungsgemeinschaft (SFB405, A9, A13), Deutsche Krebshilfe, and the BioFuture program of the Bundesministerium für Bildung und Forschung.

² Supported by Marie Curie Excellence Grant 002739.

³ To whom correspondence should be addressed. Tel.: 49-6221-564588; Fax: 49-6221-565611; E-mail: Carsten.watzl{at}urz.uni-heidelberg.de.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?