title: Protein kinase C-alpha and -delta are required for FcalphaR (CD89) trafficking to MHC class II compartments and FcalphaR-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 FcalphaR/gammagamma (CD89, human IgA receptor)-mediated internalization of immune complexes and subsequent antigen presentation. The classical and novel PKC inhibitor, Calphostin C, inhibits FcalphaR-mediated antigen presentation and interaction of MIIC and cargo vesicle (receptor and antigen). PKC-alpha, PKC-delta, and PKC-epsilon were recruited to lipid rafts following FcalphaR crosslinking, the extent of which was determined by the phenotype of the gamma chain. Mutant gamma chain with an FcgammaRIIA 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-alpha and PKC-delta, but not PKC-epsilon, were required for association of cargo vesicle and MIIC and for FcalphaR-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.
authors.affiliation: Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03756, USA.
authors.forename: Yih-Wen
authors.initials: YW
authors.lastname: Chen
authors.forename: Mark L
authors.initials: ML
authors.lastname: Lang
authors.forename: William F
authors.initials: WF
authors.lastname: Wade
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002460:Cell Line; D004705:Endocytosis / Q000502:physiology; D004789:Enzyme Activation; D005802:Genes, MHC Class II; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D051907:Lysosomal Membrane Proteins; D021962:Membrane Microdomains / Q000378:metabolism; D009281:Naphthalenes / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D021381:Protein Transport / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011961:Receptors, Fc / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D022161:Transport Vesicles / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C036832:Fc(alpha) receptor; D007527:Isoenzymes; D051907:Lysosomal Membrane Proteins; D009281:Naphthalenes; D034741:RNA, Small Interfering; D011961:Receptors, Fc; C496628:PRKCA protein, human; C497258:PRKCD protein, human; C497255:PRKCE protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; C058819:calphostin C