Proliferating Cell Nuclear Antigen as the Cell Cycle Sensor for an HLA-Derived Peptide Blocking T Cell Proliferation

摘要: Synthetic peptides corresponding to structural regions of HLA molecules are novel immunosuppressive agents. A peptide residues 65–79 the α-chain HLA-DQA03011 (DQ65–79) blocks cell cycle progression from early G1 restriction point, which inhibits cyclin-dependent kinase-2 activity and phosphorylation retinoblastoma protein. yeast two-hybrid screen identified proliferating nuclear Ag (PCNA) as a cellular ligand for this peptide, whose interaction with PCNA was further confirmed by in vitro biochemistry. Electron microscopy demonstrates that DQ65–79 enters colocalizes T nucleus vivo. Binding did not block polymerase δ (pol δ)-dependent DNA replication vitro. These findings support key role sensor reveal an unanticipated function conserved molecules.