Effects of nonapeptides derived from the N-terminal structure of human immunodeficiency virus-1 (HIV-1) Tat on suppression of CD26-dependent T cell growth.
The human immunodeficiency virus-1 (HIV-1) transactivator Tat occurs extracellularly and exerts immunosuppressive effects. Interestingly, Tat inhibits dipeptidyl peptidase IV (DP IV) activity of the T cell activation marker CD26. The short N-terminal nonapeptide Tat(1-9), MDPVDPNIE, also inhibits DP IV activity and suppresses DNA synthesis of tetanus toxoid-stimulated peripheral blood mononuclear cells (PBMC). Here, we present the influence of amino acid exchanges in the first three positions of Tat(1-9). For instance, the replacement of D2 of Tat(1-9) by G or K generated peptides, which inhibit DP IV-catalyzed IL-2(1-12) cleavage nearly threefold stronger. Similar effects were observed on the suppression of DNA synthesis of Tetanus toxoid-stimulated PBMC. This correlation suggests that Tat(1-9)-deduced peptides mediate antiproliferative effects at least in part via specific DP IV interactions and supports the hypothesis that CD26 plays a key role in the regulation of lymphocyte growth.
Wrenger
S
S
Department of Internal Medicine, Otto-von-Guericke-University, Magdeburg, Germany.
Reinhold
D
D
Faust
J
J
Mrestani-Klaus
C
C
Brandt
W
W
Fengler
A
A
Neubert
K
K
Ansorge
S
S
D000107:Acetylation; D019943:Amino Acid Substitution; D004261:DNA Replication / Q000187:drug effects; D018819:Dipeptidyl Peptidase 4 / Q000187:drug effects* / Q000502:physiology; D015696:Gene Products, tat / Q000737:chemistry* / Q000494:pharmacology*; D015497:HIV-1 / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D007668:Kidney / Q000201:enzymology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008715:Methionine / Q000737:chemistry; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013745:Tetanus Toxoid / Q000494:pharmacology; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D010446:Peptide Fragments; D015842:Serine Proteinase Inhibitors; D013745:Tetanus Toxoid; D054322:tat Gene Products, Human Immunodeficiency Virus; C415751:tat peptide (1-9), Human immunodeficiency virus 1; D018664:Interleukin-12; D008715:Methionine; D018819:Dipeptidyl Peptidase 4