THE N-TERMINAL X-X-PRO SEQUENCE OF THE HIV-1 TAT PROTEIN IS IMPORTANTFOR 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 intera ct with dipeptidyl peptidase IV (DP IV), which is identical to the T c ell activation marker CD26. Here we show that the N-terminal amino aci d sequence of Tat is essential for the inhibition of DP IV-catalyzed I L-2(1-12) degradation. N-terminal modification of Tat with rhodamine p revented inhibition of enzymatic activity of DP TV as well as suppress ion of DNA synthesis of mitogen-stimulated human T cells. Moreover, na tural peptides containing the X-X-Pro N-terminal motif of Tat also inh ibited DP TV activity. These data suggest the existence of endogenous immunomodulatory oligopeptides which influence immune cell proliferati on and differentiation via DP IV as does HIV-1 Tat.