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Blood, 1 November 2005, Vol. 106, No. 9, pp. 3074-3081.
Prepublished online as a Blood First Edition Paper on June 7, 2005; DOI 10.1182/blood-2004-10-4094.
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Submitted October 26, 2004
Accepted May 27, 2005
MHC class II/CD38/CD9: a lipid raft-dependent signaling complex in human monocytes
Marie-Therese Zilber, Niclas Setterblad, Thierry Vasselon, Christelle Doliger, Nuala Mooney, Dominique Charron, and Catherine Gelin*
Inserm U662, Institut d'Hematologie, Hopital Saint-Louis, Paris, France
Service Commun d'Imagerie, Institut d'Hematologie, Hopital Saint-Louis, Paris, France
* Corresponding author; email: gelin{at}histo.chu-stlouis.fr.
Despite a lack of signaling motifs in their cytoplasmic domain, MHC class II molecules trigger a variety of intracellular signals that regulate antigen-presenting cells function. They thus may use associated effector molecules as demonstrated on B cells and dendritic cells. The starting point of this study comes from our previous work, which demonstrated that the ecto-enzyme CD38 is functionally linked to MHC class II molecules. We report that CD38 and HLA-DR are functionally and physically associated in lipid rafts microdomains of cell surface monocytes and that the integrity of these domains is necessary for the HLA-DR and CD38 signaling events. Moreover we identified the tetraspanin CD9 molecule as a partner of the CD38/HLA-DR complex, and demonstrated that HLA-DR, CD38 and CD9 share a common pathway of tyrosine kinase activation in human monocytes. The analysis of conjugates formation between monocytes presenting superantigen and T cells shows the active participation of CD9 and HLA-DR on the monocyte surface. Together, these observations demonstrate the presence of a CD38 and HLA-DR signaling complex within tetraspanin-containing lipid rafts, and the functional impact of their molecular partner CD9 in antigen-presentation.

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