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

Citation
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
Citations number
58
Categorie Soggetti
Immunology
Journal title
ISSN journal
00221767
Volume
160
Issue
5
Year of publication
1998
Pages
2215 - 2222
Database
ISI
SICI code
0022-1767(1998)160:5<2215:IOCPBA>2.0.ZU;2-W
Abstract
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.