FcepsilonRI-mediated antigen endocytosis turns interferon-gamma-treated mouse mast cells from inefficient into potent antigen-presenting cells.
Previous studies in our laboratory have shown that bone-marrow-derived mast cells (BMMC) could present immunogenic peptides, from soluble antigens endocytosed through fluid phase, only if they were subjected to a 48-hr treatment with interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF). In contrast to GM-CSF, interferon-gamma (IFN-gamma) which highly upregulates major histocompatibility complex (MHC) class II expression, completely inhibits the generation of immunogenic peptides. We have used this model to study the role of FcepsilonRI-mediated antigen internalization in the regulation of the antigen-presenting function of IFN-gamma-treated mast cells. Here, we report that FcepsilonRI can reverse the IFN-gamma-treated mast cells from inefficient to highly efficient antigen-presenting cells. Inhibition of the antigen presenting capacity by piceatannol, a protein tyrosine kinase (PTK) syk inhibitor, indicates that this is an active process resulting from immunoglobulin E (IgE)-antigen-FcepsilonRI engagement which involves tyrosines found in the immunoreceptor tyrosine-based activation motif (ITAM) embedded in the cytoplasmic tail of the FcepsilonRI beta and gamma chains. Antigen-presenting function was also shown to require the activation of phosphatidyl inositol 3 (PI3) kinase, downstream of PTK syk phosphorylation, since this activity was completely blocked by wortmannin, a PI3 kinase inhibitor. These data suggest that signalling generated by FcepsilonRI provides mast cells with IgE-mediated enhanced antigen presentation to T cells and emphasize a so far unknown immunoregulatory mast-cell function that might take place in inflammatory sites.
Tkaczyk
C
C
Unité d'immuno-allergie, Institut Pasteur, Paris, France.
Villa
I
I
Peronet
R
R
David
B
B
Mécheri
S
S
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology; D004140:Dinitrophenols / Q000276:immunology; D004705:Endocytosis / Q000276:immunology*; D006241:Haptens / Q000276:immunology; D006863:Hydrogen-Ion Concentration; D007073:Immunoglobulin E / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology*; D008247:Lysosomes / Q000276:immunology; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008811:Mice, Inbred DBA; D010047:Ovalbumin / Q000276:immunology; D017455:Receptors, IgE / Q000276:immunology*; D011994:Recombinant Proteins
D004140:Dinitrophenols; D006241:Haptens; D017455:Receptors, IgE; D011994:Recombinant Proteins; C045521:dinitrophenol-ovalbumin; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin