FcepsilonRI-mediated antigen endocytosis turns interferon-gamma-treated mouse mast cells from inefficient into potent antigen-presenting cells.

Abstract:

: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.

journal_name

Immunology

journal_title

Immunology

authors

Tkaczyk C,Villa I,Peronet R,David B,Mécheri S

doi

10.1046/j.1365-2567.1999.00789.x

keywords:

subject

Has Abstract

pub_date

1999-06-01 00:00:00

pages

333-40

issue

2

eissn

0019-2805

issn

1365-2567

pii

imm789

journal_volume

97

pub_type

杂志文章