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

FEBS Letters

Faust, Jürgen⁴  Kraft, Margot¹  Wrenger, Sabine³  Hoffmann, Torsten²  Frank, Rainer¹  Neubert, Klaus⁴  Ansorge, Siegfried³  Reinhold, Dirk³ 

[1] Center for Molecular Biology, University of Heidelberg, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany;Hans-Knöll-Institute Jena, BMFT-Group Halle, Wolfgang-Langenbeck-Str. 3, 06120 Halle (Saale), Germany;Center for Internal Medicine, Institute of Experimental Internal Medicine, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany;Department of Biochemistry and Biotechnology, Martin-Luther-University Halle-Wittenberg, Kurt-Motkes-Str. 3, 06120 Halle (Saale), Germany

关键词: HIV-1;    Tat immunosuppressive activity;    Dipeptidyl peptidase IV;    CD26;    Pokeweed mitogen-stimulated human T cell;    Boc;    t-butyloxycarbonyl;    Fmoc;    9-fluorenylmethyloxycarbonyl;    PWM;    pokeweed mitogen;    ACTH;    adrenocorticotropic hormone;    GRP;    gastrin-releasing peptide;   

DOI  :  10.1016/0014-5793(96)00221-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown