Protein kinase C delta stimulates antigen presentation by Class II MHC in murine dendritic cells

Int Immunol. 2007 Jun;19(6):719-32. doi: 10.1093/intimm/dxm034. Epub 2007 Apr 19.

Abstract

Maturation of dendritic cells (DCs) regulates protein sorting in endosomal compartments to promote the surface expression of molecules involved in T cell activation. MHC Class II complexes are mobilized to the surface via intracellular effector molecules that remain largely unknown. We here show that protein kinase C (PKC) stimulates Class II antigen surface expression, using knock-in mice that express a Class II-green fluorescent protein fusion protein as a read out. Selective inhibition of PKCdelta counteracts the ability of DCs to stimulate Class II MHC-restricted antigen-specific T cells. Activation of PKC does not affect antigen uptake, peptide loading and surface display of Class I MHC and transferrin receptor in DCs. We show that activation-induced Class II MHC surface expression is dependent on activation of PKCdelta and conclude that this event is pivotal for optimal CD4 T cell activation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetophenones / pharmacology
  • Animals
  • Antigen Presentation / drug effects
  • Antigen Presentation / immunology*
  • Benzopyrans / pharmacology
  • Blotting, Western
  • Cell Membrane / metabolism
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Endocytosis / drug effects
  • Endocytosis / immunology
  • Enzyme Inhibitors / pharmacology
  • Flow Cytometry
  • Gene Expression
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / metabolism*
  • Ionomycin / pharmacology
  • Lipopolysaccharides / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Phosphorylation / drug effects
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism
  • Protein Kinase C-delta / antagonists & inhibitors
  • Protein Kinase C-delta / genetics
  • Protein Kinase C-delta / metabolism*
  • Protein Transport / drug effects
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Acetophenones
  • Benzopyrans
  • Enzyme Inhibitors
  • Histocompatibility Antigens Class II
  • Lipopolysaccharides
  • Green Fluorescent Proteins
  • Ionomycin
  • rottlerin
  • Protein Kinase C
  • Protein Kinase C-delta
  • Tetradecanoylphorbol Acetate