CD26 mediates dissociation of Tollip and IRAK-1 from caveolin-1 and induces upregulation of CD86 on antigen-presenting cells.

CD26 is a T-cell costimulatory molecule with dipeptidyl peptidase IV enzyme activity in its extracellular region. We have previously reported that the addition of recombinant soluble CD26 resulted in enhanced proliferation of human T lymphocytes induced by the recall antigen tetanus toxoid (TT) via upregulation of CD86 on monocytes and ...
that caveolin-1 was a binding protein of CD26, and the CD26-caveolin-1 interaction resulted in caveolin-1 phosphorylation (p-cav-1) as well as TT-mediated T-cell proliferation. However, the mechanism involved in this immune enhancement has not yet been elucidated. In the present work, we perform experiments to identify the molecular mechanisms by which p-cav-1 leads directly to the upregulation of CD86. Through proteomic analysis, we identify Tollip (Toll-interacting protein) and IRAK-1 (interleukin-1 receptor-associated serine/threonine kinase 1) as caveolin-1-interacting proteins in monocytes. We also demonstrate that following stimulation by exogenous CD26, Tollip and IRAK-1 dissociate from caveolin-1, and IRAK-1 is then phosphorylated in the cytosol, leading to the upregulation of CD86 via activation of NF-kappaB. Binding of CD26 to caveolin-1 therefore regulates signaling pathways in antigen-presenting cells to induce antigen-specific T-cell proliferation.
Mesh Terms:
Animals, Antigen-Presenting Cells, Antigens, CD, Antigens, CD86, Caveolin 1, Caveolins, Cell Line, Cell Membrane, Cell Proliferation, Cercopithecus aethiops, Dipeptidyl Peptidase 4, Humans, Interleukin-1 Receptor-Associated Kinases, Intracellular Signaling Peptides and Proteins, Membrane Glycoproteins, Monocytes, Phosphotyrosine, Promoter Regions, Genetic, Protein Binding, Protein Kinases, RNA, Small Interfering, T-Lymphocytes, Tetanus Toxoid, Up-Regulation
Mol. Cell. Biol.
Date: Sep. 01, 2005
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