INHIBITION OF CELL-CYCLE PROGRESSION BY A SYNTHETIC PEPTIDE CORRESPONDING TO RESIDUES-65-79 OF AN HLA CLASS-II SEQUENCE - FUNCTIONAL SIMILARITIES BUT MECHANISTIC DIFFERENCES WITH THE IMMUNOSUPPRESSIVE DRUG RAPAMYCIN
Ml. Boytim et al., INHIBITION OF CELL-CYCLE PROGRESSION BY A SYNTHETIC PEPTIDE CORRESPONDING TO RESIDUES-65-79 OF AN HLA CLASS-II SEQUENCE - FUNCTIONAL SIMILARITIES BUT MECHANISTIC DIFFERENCES WITH THE IMMUNOSUPPRESSIVE DRUG RAPAMYCIN, The Journal of immunology, 160(5), 1998, pp. 2215-2222
A synthetic peptide corresponding to a region of the alpha(1) alpha-he
lix of DQA03011 (DQ 65-79) inhibits the proliferation of human PBL and
T cells in an allele-nonspecific manner. It blocks proliferation stim
ulated by anti-CD3 mAb, PHA-P, and alloantigen, but not by PMA and ion
omycin. Substitution of each amino add with serine shows that residues
66, 68, 69, 71-73, and 75-79 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 bl
ock proliferation. The DQ 65-79 peptide does not affect expression of
IL-2 or IL-2R; however, IL-2-stimulated proliferation is inhibited. Ce
ll cycle progression is blocked at the G(1)/S transition, and the acti
vity of cdk2 (cyclin-dependent kinase 2) kinase is impaired by the con
tinued presence of p27. Although these results suggest a mechanism sim
ilar to that of rapamycin, the peptide inhibition is not reversed with
FK-506, which indicates a distinct mechanism.