The N-terminal X-X-Pro sequence of the HIV-1 Tat protein is important for the inhibition of dipeptidyl peptidase IV (DP IV/CD26) and the suppression of mitogen-induced proliferation of human T cells.
Recent data in the literature suggest that the HIV-1 Tat(1-86) protein exhibits immunosuppressive effects. Moreover, Tat was found to interact with dipeptidyl peptidase IV (DP IV), which is identical to the T cell activation marker CD26. Here we show that the N-terminal amino acid sequence of Tat is essential for the inhibition of DP IV-catalyzed IL-2(1-12) degradation. N-terminal modification of Tat with rhodamine prevented inhibition of enzymatic activity of DP IV as well as suppression of DNA synthesis of mitogen-stimulated human T cells. Moreover, natural peptides containing the X-X-Pro N-terminal motif of Tat also inhibited DP IV activity. These data suggest the existence of endogenous immunomodulatory oligopeptides which influence immune cell proliferation and differentiation via DP IV as does HIV-1 Tat.
Wrenger
S
S
Center for Internal Medicine, Institute of Experimental Internal Medicine, Otto-von-Guericke University Magdeburg, Germany.
Reinhold
D
D
Hoffmann
T
T
Kraft
M
M
Frank
R
R
Faust
J
J
Neubert
K
K
Ansorge
S
S
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D015696:Gene Products, tat / Q000737:chemistry / Q000494:pharmacology*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007668:Kidney; D008213:Lymphocyte Activation; D008934:Mitogens / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013552:Swine; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D007376:Interleukin-2; D008934:Mitogens; D009842:Oligopeptides; D011480:Protease Inhibitors; D054322:tat Gene Products, Human Immunodeficiency Virus; D018819:Dipeptidyl Peptidase 4