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J. Biol. Chem., Vol. 279, Issue 32, 33875-33881, August 6, 2004

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Modulation of FcRI (CD64) Ligand Binding by Blocking Peptides of Periplakin^*

Jeffrey M. Beekman, Jantine E. Bakema, Joke van der Linden, Bastiaan Tops, Marja Hinten, Martine van Vugt¶, Jan G. J. van de Winkel¶, and Jeanette H. W. Leusen||

From the Immunotherapy Laboratory, Department of Immunology, University Medical Center Utrecht, Lundlaan 6, 3584 EA, The Netherlands, Medarex Europe, Lundlaan 6, 3584 EA, Utrecht, The Netherlands, and ^¶Genmab, Yalelaan 60, 3584 CM, Utrecht, The Netherlands

FcRI requires both the intracellular domain of the -chain and associated leukocyte Fc receptor (FcR) -chains for its biological function. We recently found the C terminus of periplakin to selectively interact with the cytoplasmic domain of the FcRI -chain. It thereby enhances the capacity of FcRI to bind, internalize, and present antigens on MHC class II. Here, we characterized the domains involved in FcRI-periplakin interaction using truncated and alanine-substituted FcRI mutants and randomly mutagenized periplakin. This allowed us to design TAT peptides that selectively interfered with endogenous FcRI-periplakin interactions. The addition of these peptides to FcRI-expressing cells modulated FcRI ligand binding, as assessed by erythrocyte-antibody-rosetting. These data support a dominant-negative role of C-terminal periplakin for FcRI biological activity and implicate periplakin as a novel regulator of FcRI in immune cells.

Received for publication, January 29, 2004 , and in revised form, May 20, 2004.

^* This work was supported by Dutch Science Foundation (NWO) Grant 901-07-229 (to J. H. W. L.) and by Medarex Europe (to J. M. B. and J. E. B.). 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.

^|| To whom correspondence should be addressed: Immunotherapy Laboratory, Dept. of Immunology, Lundlaan 6, KC.02-085.2, University Medical Center Utrecht, 3584 EA, Utrecht. Tel.: 31-30-2504268; Fax: 31-30-2504305; E-mail: J.H.W.Leusen{at}lab.azu.nl.

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