Proliferating cell nuclear antigen as the cell cycle sensor for an HLA- derived peptide blocking T cell proliferation

Xuefeng Ling, Salar Kamangar, Michelle L. Boytim, Zvi Kelman, Philip Huie, Shu Chen Lyu, Richard K. Sibley, Jerard Hurwitz, Carol Clayberger, Alan M. Krensky*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)6188-6192
Number of pages5
JournalJournal of Immunology
Volume164
Issue number12
DOIs
StatePublished - Jun 15 2000

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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