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Prepublished online as a Blood First Edition Paper on May 29, 2003; DOI 10.1182/blood-2003-01-0273. This Article Full Text (PDF) All Versions of this Article: 2003-01-0273v1 102/6/2130    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Andreae, S. Articles by Triebel, F. Search for Related Content PubMed PubMed Citation Articles by Andreae, S. Articles by Triebel, F. Social Bookmarking                   What's this? Submitted February 7, 2003 Accepted April 28, 2003 MHC class II signal transduction in human dendritic cells induced by a natural ligand, the LAG-3 protein (CD223) Susanne Andreae, Sandrine Buisson, and Frederic Triebel* Faculte de Pharmacie, Universite Paris-Sud, Chatenay-Malabry, France * Corresponding author; email: Frederic.Triebel{at}cep.u-psud.fr. Upon encountering a danger signal, DCs undergo a complex maturation process and become specialized in antigen presentation. We previously reported that engagement of MHC class II molecules located on immature DCs in membrane rafts by LAG-3 (CD223) leads to DC maturation. In contrast, exposure of DC to class II-specific mAb did not lead to maturation. Here we have investigated the signal transduction pathways involved in the LAG-3-induced maturation of human monocyte-derived DCs. We first show that areas of raft aggregation (both cholesterol-rich and CDw78 microdomains) could be visualized using a soluble LAG-3 protein and confocal microscopy. Engagement of class II by both its natural ligand LAG-3 and class II mAb induces rapid protein phosphorylation of PLC2 and p72syk as well as activation of phosphatidyl inositol 3-kinase /Akt, p42/44 extra-cellular signal-regulated protein kinase and p38 mitogen-activated protein kinase pathways. Studies using inhibitors demonstrate that these three pathways are all important in inducing the maturation process of LAG-3-stimulated DCs. When class II molecules were ligated with LAG-3 versus specific antibody, differences in the phosphorylation pattern of c-Akt were observed. Thus, MHC class II signaling in DCs involves several pathways that have to be finely regulated to lead to cell activation and maturation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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