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Fcα Receptor Cross-Linking Causes Translocation of Phosphatidylinositol-Dependent Protein Kinase 1 and Protein Kinase Bα to MHC Class II Peptide-Loading-Like Compartments1

A20 IIA1.6 B cells cotransfected with FcαR and wild-type γ-chain (wt-ITAM (immunoreceptor tyrosine-based activation motif)) or FcαR and γ-chain, in which the wt-ITAM was substituted with the FcγRIIA ITAM (IIA-ITAM), were used to investigate cell signaling events influencing presentation of FcαR-targeted exogenous Ag in the context of MHC class II. wt-ITAM cells presented FcαR-targeted OVA more efficiently than IIA-ITAM transfectants to OVA-specific T cell hybridomas. Phosphatidylinositol 3-kinase (PI 3-kinase) inhibition abrogated Ag presentation, suggesting that FcαR may trigger a PI 3-kinase-dependent signal transduction pathway, and thus phosphatidylinositol-dependent protein kinase (PDK1) and protein kinase B α (PKBα) activation. Cross-linking FcαR on wt-ITAM or IIA-ITAM cells triggered equivalent PI 3-kinase-dependent activation of PKBα. Furthermore, FcαR cross-linking triggered recruitment of PDK1 and serine-phosphorylated PKBα to capped cell surface FcαR irrespective of the γ-chain ITAM. Although FcαR endocytosis was accompanied by translocation of PDK1 and phospho-PKBα to FcαR-containing vesicles in both transfectants, this was decreased in IIA-ITAM cells, and a significant proportion of PDK1 and PKBα remained at the plasma membrane. In wt-ITAM cells, PDK1 and serine-phosphorylated PKBα translocated to lysosomal-associated membrane glycoprotein 1- and cathepsin B-containing vesicles, consistent with MHC class II peptide-loading compartments (MIIC) described by other groups. Our data indicate that translocation of signal transduction mediators to MIIC-like compartments accompanies efficient presentation of receptor-targeted Ag, and suggest a mechanism connecting signaling to the Ag-processing pathway.