FcεRI-mediated antigen endocytosis turns interferon-γ-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-γ (IFN-γ) 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 FcεRI-mediated antigen internalization in the regulation of the antigen-presenting function of IFN-γ-treated mast cells. Here, we report that FcεRI can reverse the IFN-γ-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–FcεRI engagement which involves tyrosines found in the immunoreceptor tyrosine-based activation motif (ITAM) embedded in the cytoplasmic tail of the FcεRI β and γ 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 FcεRI 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