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FcεRI‐mediated antigen endocytosis turns interferon‐γ‐treated mouse mast cells from inefficient into potent antigen‐presenting cells
Author(s) -
Christine Tkaczyk,
Irène Villa,
Roger Péronet,
B. David,
Salaheddine Mécheri
Publication year - 1999
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1999.00789.x
Subject(s) - syk , antigen , microbiology and biotechnology , antigen presentation , antigen processing , interferon gamma , mast cell , cross presentation , immunoglobulin e , biology , chemistry , major histocompatibility complex , immune system , antibody , tyrosine kinase , immunology , mhc class i , t cell , signal transduction
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.