CD26 Up-Regulates Expression of CD86 on Antigen-Presenting Cells by Means of Caveolin-1

• Published in: Proceedings of the National Academy of Sciences - PNAS 2004-09, Vol.101 (39), p.14186-14191
• Main Authors: Ohnuma, Kei, Yamochi, Tadanori, Uchiyama, Masahiko, Nishibashi, Kunika, Yoshikawa, Noritada, Shimizu, Noriaki, Iwata, Satoshi, Tanaka, Hirotoshi, Dang, Nam H., Morimoto, Chikao, Schlossman, Stuart F.
• Format: Article
• Language: English
• Subjects: Animals; Antigen presenting cells; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - metabolism; Antigens, CD - biosynthesis; B7-2 Antigen; Biological Sciences; Caveolae; Caveolin 1; Caveolins - deficiency; Caveolins - genetics; Caveolins - immunology; Caveolins - metabolism; Cell Line; Cell lines; Cercopithecus aethiops; COS Cells; Dipeptidyl Peptidase 4 - drug effects; Dipeptidyl Peptidase 4 - physiology; Gene expression; HEK293 cells; Humans; Immunology; Immunoprecipitation; Lymphocyte Activation - immunology; Membrane Glycoproteins - biosynthesis; Molecules; Monocytes; Monocytes - cytology; Monocytes - immunology; Monocytes - metabolism; NF-kappa B - metabolism; Phosphorylation; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Recombinant Proteins - immunology; Recombinant Proteins - metabolism; RNA, Small Interfering - pharmacology; Small interfering RNA; T lymphocytes; T-Lymphocytes - cytology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Tetanus Toxoid - immunology; Up regulation; Up-Regulation - immunology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0405266101

CD26 is a T cell costimulatory molecule with dipeptidyl peptidase IV activity in its extracellular region. We previously reported that recombinant soluble CD26 enhanced T cell proliferation induced by the recall antigen tetanus toxoid (TT). However, the mechanism involved in this enhancement is not yet elucidated. We now demonstrate that CD26 binds Caveolin-1 on antigen-presenting cells, and that residues 201-211 of CD26 along with the serine catalytic site at residue 630 contribute to binding to caveolin-1 scaffolding domain. In addition, after CD26-caveolin-1 interaction on TT-loaded monocytes, caveolin-1 is phosphorylated, which links to activate NF-κB, followed by up-regulation of CD86. Finally, reduced caveolin-1 expression on monocytes inhibits CD26-mediated CD86 up-regulation and abrogates CD26 effect on TT-induced T cell proliferation. Taken together, these results strongly suggest that CD26-caveolin-1 interaction plays a role in the up-regulation of CD86 on TT-loaded monocytes and subsequent engagement with CD28 on T cells, leading to antigen-specific T cell activation.