Protein kinase C-α and -δ are required for FcαR (CD89) trafficking to MHC class II compartments and FcαR-mediated antigen presentation

Abstract

Studies have demonstrated that receptor-mediated signaling, receptor/antigen complex trafficking, and major histocompatibility complex class II compartments (MIIC) are critically related to antigen presentation to CD4+ T cells. In this study, we investigated the role of protein kinase C (PKC) in FcαR/γγ (CD89, human IgA receptor)mediated internalization of immune complexes and subsequent antigen presentation. The classical and novel PKC inhibitor, Calphostin C, inhibits FcαR-mediated antigen presentation and interaction of MIIC and cargo vesicle (receptor and antigen). PKC-α), PKC-δ, and PKC-E were recruited to lipid rafts following Fcα R crosslinking, the extent of which was determined by the phenotype of the γ chain. Mutant y chain with an FcγRIIA ITAM (immunoreceptor tyrosine-based activation motif) insert was less able to recruit PKC and trigger antigen presentation. Both PKC isoform-specific peptide inhibitors and short interfering RNA (siRNA) showed that PKC-α and PKC-δ, but not PKC-E, were required for association of cargo vesicle and MIIC and for FcαR-mediated and soluble antigen presentation. Inhibition of PKC (classical and novel) did not alter major histocompatibility class II biosynthesis, assembly, transport, or plasma membrane stability. PKC's role in facilitating interaction of cargo vesicle and MIIC is likely due to regulation of vesicle biology required for fusion of cargo vesicles to MIIC. Copyright © Blackwell Munksgaard 2004.