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Blood, 15 August 2004, Vol. 104, No. 4, pp. 1183-1190.
Prepublished online as a Blood First Edition Paper on May 6, 2004; DOI 10.1182/blood-2004-01-0104.


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Submitted January 13, 2004
Accepted April 13, 2004

CD63 Tetraspanin slows down cell migration and translocates to the endosomal/lysosomal/MIICs route after extracellular stimuli in human immature dendritic cells

Adriana R Mantegazza, Maria M Barrio, Sandrine Moutel, Laura Bover, Markus Weck, Peter Brossart, Jean-Luc Teillaud, and Jose Mordoh*

Fundacion Instituto Leloir, Buenos Aires, Argentina
Centro de Investigaciones Oncologicas-Fundacion Cancer, Buenos Aires, Argentina
Centre de Recherches Biomedicales des Cordeliers, Unite INSERM 255, Paris, France
Fundacion Instituto Leloir, Buenos Aires, Argentina; Centro de Investigaciones Oncologicas-Fundacion Cancer, Buenos Aires, Argentina
Department of Internal Medicine, University of Tubingen, Tubingen, Germany

* Corresponding author; email: jmordoh{at}leloir.org.ar.

We analyzed herein whether members of the Tetraspanin superfamily are involved in human immature dendritic cells (DCs) functions such as foreign antigens internalization, phagocytosis and cell migration. We show that CD63, CD9, CD81, CD82 and CD151, are present in immature DCs. Whereas CD9 and CD81 are mostly expressed at the cell surface, CD63 and CD82 are also located in intracellular organelles. Complexes of monoclonal antibody (Mab) FC-5.01-CD63 or Fab-5.01-CD63 were rapidly translocated "outside-in" and followed the endocytic pathway through early endosomes and lysosomes, reaching MIICs in less than 1 hour. Internalization of CD63 was also observed during Saccharomyces cerevisiae phagocytosis. Moreover, an association of CD63 with the {beta}-glycan receptor dectin-1 was observed. Mabs against CD9, CD63, CD81 and CD82 enhanced by 50% the migration induced by the chemokines MIP-5 and MIP-1{alpha}. Concomitantly, Mabs against CD63 and CD82 diminished the surface expression of CD29, CD11b, CD18 and {alpha}5 integrins. By immunoprecipitation experiments we found that CD63 associated with integrins CD11b and CD18. These results suggest that CD9, CD63, CD81 and CD82 could play a role in modulating the interactions between immature DCs and their environment, slowing their migratory ability. However, only CD63 would intervene in the internalization of complex antigens.


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