CD26 up-regulates expression of CD86 on antigen-presenting cells by means of caveolin-1.
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-kappaB, 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.
Ohnuma
Kei
K
Department of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-Ku, Tokyo 108-8639, Japan.
Yamochi
Tadanori
T
Uchiyama
Masahiko
M
Nishibashi
Kunika
K
Yoshikawa
Noritada
N
Shimizu
Noriaki
N
Iwata
Satoshi
S
Tanaka
Hirotoshi
H
Dang
Nam H
NH
Morimoto
Chikao
C
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism*; D015703:Antigens, CD / Q000096:biosynthesis*; D051940:B7-2 Antigen; D019556:COS Cells; D051242:Caveolin 1; D022461:Caveolins / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D018819:Dipeptidyl Peptidase 4 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000494:pharmacology; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013745:Tetanus Toxoid / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology*
D015703:Antigens, CD; D051940:B7-2 Antigen; C495540:CAV1 protein, human; C497964:CD86 protein, human; D051242:Caveolin 1; D022461:Caveolins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D013745:Tetanus Toxoid; D018819:Dipeptidyl Peptidase 4