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J. Biol. Chem., Vol. 281, Issue 11, 7075-7081, March 17, 2006

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Identification of a Polymeric Ig Receptor Binding Phage-displayed Peptide That Exploits Epithelial Transcytosis without Dimeric IgA Competition^*

Ranveig Braathen¹, Anders Sandvik², Gøril Berntzen, Sven Hammerschmidt^¶, Burkhard Fleckenstein^||, Inger Sandlie, Per Brandtzaeg, Finn-Eirik Johansen³, and Vigdis Lauvrak³⁴

From the Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), Institute of Pathology, University of Oslo, Rikshospitalet University Hospital, N-0027 Oslo, Norway, Department of Molecular Biosciences, University of Oslo, N-0316 Oslo, Norway, ^¶Research Center for Infectious Diseases, University of Würzburg, D-97070 Würzburg, Germany, and the ^||Institute of Immunology, University of Oslo, Rikshospitalet University Hospital, N-0027 Oslo, Norway

The polymeric Ig receptor (pIgR), also called membrane secretory component (SC), mediates epithelial transcytosis of polymeric immunoglobulins (pIgs). J Chain-containing polymeric IgA (pIgA) and pentameric IgM bind pIgR at the basolateral epithelial surface. After transcytosis, the extracellular portion of the pIgR is cleaved at the apical side, either complexed with pIgs as bound SC or unoccupied as free SC. This transport pathway may be exploited to target bioactive molecules to the mucosal surface. To identify small peptide motifs with specific affinity to human pIgR, we used purified free SC and selection from randomized, cysteine-flanked 6- and 9-mer phage-display libraries. One of the selected phages, called C9A, displaying the peptide CVVWMGFQQVC, showed binding both to human free SC and SC complexed with pIgs. However, the pneumococcal surface protein SpsA (Streptococcus pneumoniae secretory IgA-binding protein), which binds human SC at a site distinct from the pIg binding site, competed with the C9A phage for binding to SC. The C9A phage showed greatly increased transport through polarized Madin-Darby canine kidney cells transfected with human pIgR. This transport was not affected by pIgA nor did it inhibit pIgR-mediated pIgA transcytosis. A free peptide of identical amino acid sequence as that displayed by the C9A phage inhibited phage interaction with SC. This implied that the C9A peptide sequence may be exploited for pIgR-mediated epithelial transport without interfering with secretory immunity.

Received for publication, August 3, 2005 , and in revised form, January 6, 2006.

^* This work was supported by the Research Council of Norway, the Foundation of Health and Rehabilitation, and the Norwegian Health Association. 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.

² Present address: LIIPAT, University of Oslo, Rikshospitalet University Hospital, N-0027 Oslo, Norway.

³ Both authors are senior co-authors.

⁴ Present address: Dept. of Microbiology, Akershus University Hospital, N-1478 Lørens-kog, Norway.

¹ To whom correspondence should be addressed. Tel.: 47-23071485; Fax: 47-23071511; E-mail: ranveig.braathen{at}medisin.uio.no.

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