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Originally published In Press as doi:10.1074/jbc.M310528200 on December 3, 2003

J. Biol. Chem., Vol. 279, Issue 8, 6296-6304, February 20, 2004
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Ectodomains 3 and 4 of Human Polymeric Immunoglobulin Receptor (hpIgR) Mediate Invasion of Streptococcus pneumoniae into the Epithelium*

Christine Elm{ddagger}§, Ranveig Braathen§, Simone Bergmann{ddagger}||, Ronald Frank{ddagger}, Jean-Pierre Vaerman**, Charlotte S. Kaetzel{ddagger}{ddagger}, Gursharan S. Chhatwal{ddagger}, Finn-Eirik Johansen¶, and Sven Hammerschmidt{ddagger}||§§

From the {ddagger}GBF-German Research Centre for Biotechnology, Braunschweig 38124, Germany, the Institute of Pathology, Laboratory for Immunohistochemistry and Immunopathology, University of Oslo, Rikshospitalet, Oslo 0027, Norway, the ||Research Center for Infectious Diseases, University of Würzburg, Würzburg 97070, Germany, the **Experimental Medicine Unit, ICP, Université Catholique de Louvain, Brussels 1200, Belgium, the {ddagger}{ddagger}Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington Kentucky 40536-0298

Streptococcus pneumoniae binds to the ectodomain of the human polymeric Ig receptor (pIgR), also known as secretory component (SC), via a hexapeptide motif in the choline-binding protein SpsA. The SpsA-pIgR interaction mediates adherence and internalization of the human pathogen into epithelial cells. In this study the results of SpsA binding to human, mouse, and chimeric SC strongly supported the human specificity of this unique interaction and suggested that binding sites in the third and fourth Ig-like domain of human SC (D3 and D4, respectively) are involved in SpsA-pIgR complex formation. Binding of SpsA to SC-derived synthetic peptides indicated surface-located potential binding motifs in D3 and D4. Adherence and uptake of pneumococci or SpsA-coated latex beads depended on the SpsA hexapeptide motif as well as SpsA-binding sites in D3 and D4 of human pIgR. The involvement of D3 and D4 in adherence and invasion was demonstrated by the lack of binding of SpsA-coated latex beads to transfected epithelial cells expressing mutated pIgR. Finally, blocking experiments with chimeric human-mouse SC as well as synthetic peptides indicated the participation of D3 and a key role of D4 in pneumococcal invasion.


Received for publication, September 23, 2003 , and in revised form, October 29, 2003.

* This work was supported in part by Deutsche Forschungsgemeinschaft Sonderforschungsbereich Grant 587/479, Teilprojekt A6/A7 (to S. H.), the Bundesministerium für Bildung und Forschung (CAPNetz to S. H. and G. S. C.), and the Research Council of Norway (to R. B. and F.-E. J.). 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 Fig. 5S.

§ Both authors contributed equally to this work.

§§ To whom correspondence should be addressed: Research Center for Infectious Diseases, University of Würzburg, Röntgenring 11, Würzburg D-97070, Germany. Tel.: 49-931-31-2153; Fax: 49-931-31-2578; E-mail: s.hammerschmidt{at}mail.uni-wuerzburg.de.


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