Fc alpha receptor cross-linking causes translocation of phosphatidylinositol-dependent protein kinase 1 and protein kinase B alpha to MHC class II peptide-loading-like compartments
Ml. Lang et al., Fc alpha receptor cross-linking causes translocation of phosphatidylinositol-dependent protein kinase 1 and protein kinase B alpha to MHC class II peptide-loading-like compartments, J IMMUNOL, 166(9), 2001, pp. 5585-5593
A20 IIA1.6 B cells cotransfected with Fc alphaR and wild-type gamma -chain
(wt-ITAM (immunoreceptor tyrosine-based activation motif)) or Fc alphaR and
gamma -chain, in which the wt-ITAM was substituted with the Fc gamma RIIA
ITAM (IIA-ITAM), were used to investigate cell signaling events influencing
presentation of Fc alphaR-targeted exogenous Ag in the context of MHC clas
s II. wt-ITAM cells presented Fc alphaR-targeted OVA more efficiently than
IIA-ITAM transfectants to OVA-specific T cell hybridomas. Phosphatidylinosi
tol 3-kinase (PI 3-kinase) inhibition abrogated Ag presentation, suggesting
that Fc alphaR may trigger a PI 3-kinase-dependent signal transduction pat
hway, and thus phosphatidylinositol-dependent protein kinase (PDK1) and pro
tein kinase B alpha (PKB alpha) activation. Cross-linking Fc alphaR on wt-I
TAM or IIA-ITAM cells triggered equivalent PI 3-kinase-dependent activation
of PKBa. Furthermore, Fc alphaR cross-linking triggered recruitment of PDK
I and serine-phosphorylated PKB alpha to capped cell surface FcaR irrespect
ive of the gamma -chain ITAM. Although FcaR endocytosis was accompanied by
translocation of PDK1 and phospho-PKB alpha to Fe alphaR-containing vesicle
s in both transfectants, this was decreased in IIA-ITAM cells, and a signif
icant proportion of PDK1 and PKBa remained at the plasma membrane. In wt-IT
AM cells, PDK1 and serine-phosphorylated PKBa translocated to lysosomal-ass
ociated membrane glycoprotein 1- and cathepsin B-containing vesicles, consi
stent with MHC class II peptide-loading compartments (MIIC) described by ot
her groups. Our data indicate that translocation of signal transduction med
iators to MIIC-like compartments accompanies efficient presentation of rece
ptor-targeted Ag, and suggest a mechanism connecting signaling to the Ag-pr
ocessing pathway.