MHC class II/CD38/CD9: a lipid-raft-dependent signaling complex in human monocytes.
Despite a lack of signaling motifs in their cytoplasmic domain, major histocompatibility complex (MHC) class II molecules trigger a variety of intracellular signals that regulate antigen-presenting cell 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 human leukocyte antigen-DR (HLA-DR) are functionally and physically associated in lipid rafts microdomains of cellsurface 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 conjugate 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.
Zilber
Marie-Thérèse
MT
Institut National de la Santé et de la Recherche Médicale (INSERM) U662, and Service Commun d'Imagerie, Institut d'Hématologie, Hôpital SaintLouis, Paris, France.
Setterblad
Niclas
N
Vasselon
Thierry
T
Doliger
Christelle
C
Charron
Dominique
D
Mooney
Nuala
N
Gelin
Catherine
C
D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D019000:Phosphotyrosine / Q000378:metabolism; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051572:Proto-Oncogene Proteins c-hck / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism; D060245:Tetraspanin 29; D019061:src-Family Kinases / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C554869:CD9 protein, human; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D060245:Tetraspanin 29; D019000:Phosphotyrosine; C496631:HCK protein, human; D051572:Proto-Oncogene Proteins c-hck; C053102:proto-oncogene proteins c-fgr; D019061:src-Family Kinases; D051997:ADP-ribosyl Cyclase 1; D002118:Calcium