Document 0066
 DOCN  M9480066
 TI    Human immunodeficiency virus 1 Tat binds to dipeptidyl aminopeptidase IV
       (CD26): a possible mechanism for Tat's immunosuppressive activity.
 DT    9410
 AU    Gutheil WG; Subramanyam M; Flentke GR; Sanford DG; Munoz E; Huber BT;
       Bachovchin WW; Department of Biochemistry, Tufts University School of
       Medicine,; Boston, MA 02111.
 SO    Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6594-8. Unique Identifier :
       AIDSLINE MED/94294425
 AB    The human immunodeficiency virus 1 (HIV-1) Tat protein suppresses
       antigen-induced, but not mitogen-induced, activation of human T cells
       when added to T-cell cultures [Viscidi, R. P., Mayur, K., Lederman, H.
       M. & Frankel, A. D. (1989) Science 246, 1606-1608]. This activity is
       potentially pertinent to the development of AIDS because lymphocytes
       from HIV-infected individuals exhibit a similar antigen-specific
       dysfunction. Here we report that Tat binds with high affinity to the
       T-cell activation molecule dipeptidyl aminopeptidase IV (DP IV), also
       known as CD26. This molecule occurs on the surface of CD4+ cells
       responsible for the recall antigen response and appears to play an
       essential role in this response. Tat binds to both the cell surface and
       soluble forms of DP IV at physiological salt concentrations without
       inhibiting the protease activity of DP IV against small chromogenic
       substrates used to assay activity, but Tat markedly inhibits the
       activity of DP IV at lower salt concentrations. The kinetics of
       inhibition indicate the affinity of Tat for DP IV varies from 20 pM to
       11 nM, and the activity of the Tat-DP IV complex varies from 13% to
       100%, as the NaCl concentration varies from 0 to 140 mM. Cytofluorometry
       experiments demonstrate that Tat competes with anti-Ta1, a monoclonal
       antibody (mAb) specific for DP IV, for binding to cell surface DP IV,
       thus indicating that Tat binds DP IV at or near the Ta1 epitope.
       Moreover, the anti-Ta1 mAb blocks the immunosuppressive activity of Tat.
       The high affinity of Tat for DP IV, previous evidence implicating DP IV
       in antigen-specific T-cell activation events, and the ability of
       anti-Ta1 mAb to block the immunosuppressive effect of Tat make DP IV a
       plausible receptor for Tat's immunosuppressive activity.
 DE    Acquired Immunodeficiency Syndrome/IMMUNOLOGY/MICROBIOLOGY  Antigens,
       Differentiation, T-Lymphocyte/*METABOLISM  Dipeptidyl
       Peptidases/*METABOLISM  Flow Cytometry  Gene Products,
       tat/BIOSYNTHESIS/ISOLATION & PURIF/*METABOLISM  Human  HIV-1/*METABOLISM
       Kinetics  Mathematics  Models, Theoretical  Protein Binding  Recombinant
       Proteins/BIOSYNTHESIS/ISOLATION & PURIF/METABOLISM
       T-Lymphocytes/*IMMUNOLOGY/MICROBIOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).