MHC class II/CD38/CD9: a lipid-raft–dependent signaling complex in human monocytes

• Published in: Blood 2005-11, Vol.106 (9), p.3074-3081
• Main Authors: Zilber, Marie-Thérèse, Setterblad, Niclas, Vasselon, Thierry, Doliger, Christelle, Charron, Dominique, Mooney, Nuala, Gelin, Catherine
• Format: Article
• Language: English
• Subjects: ADP-ribosyl Cyclase 1 - metabolism; Antibodies, Monoclonal - immunology; Antigens, CD - metabolism; Biological and medical sciences; Calcium - metabolism; Cell Proliferation; Cells, Cultured; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Histocompatibility Antigens Class II - metabolism; Humans; Immunobiology; Membrane Glycoproteins - metabolism; Membrane Microdomains - metabolism; Monocytes - metabolism; Monocytes, macrophages; Myeloid cells: ontogeny, maturation, markers, receptors; Phosphotyrosine - metabolism; Protein Binding; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-hck - metabolism; Signal Transduction; src-Family Kinases - metabolism; T-Lymphocytes - metabolism; Tetraspanin 29
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2004-10-4094

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.