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

Michelle L. Boytim, Shu Chen Lyu, Ron Jung, Alan M. Krensky, Carol Clayberger*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

A synthetic peptide corresponding to a region of the α1 α-helix of DQA03011 (DQ 65-79) 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, 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 block proliferation. The DQ 65-79 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.

Original languageEnglish (US)
Pages (from-to)2215-2222
Number of pages8
JournalJournal of Immunology
Volume160
Issue number5
StatePublished - Mar 1 1998

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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