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*
Department of Cardiothoracic Surgery and
Division of Immunology and Transplantation Biology/Department of Pediatrics, Stanford University, Stanford, CA 94305
A synthetic peptide corresponding to a region of the
1
-helix of DQA03011 (DQ 6579) inhibits the
proliferation of human PBL and T cells in an allele-nonspecific manner.
It blocks proliferation stimulated by anti-CD3 mAb, PHA-P, and
alloantigen, but not by PMA and ionomycin. Substitution of each amino
acid with serine shows that residues 66, 68, 69, 7173, and 7579 are
critical for function. Inhibition of proliferation is long lasting and
is not reversible with exogenous IL-2. The peptide can be added 24 to
48 h after stimulation and still block proliferation. The DQ
6579 peptide does not affect expression of IL-2 or IL-2R; however,
IL-2-stimulated proliferation is inhibited. Cell cycle progression is
blocked at the G1/S transition, and the activity of cdk2
(cyclin-dependent kinase 2) kinase is impaired by the continued
presence of p27. Although these results suggest a mechanism similar to
that of rapamycin, the peptide inhibition is not reversed with FK-506,
which indicates a distinct mechanism.
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