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M9480066.TXT
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1994-08-09
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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).