HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Boytim, M. L. Articles by Clayberger, C. Search for Related Content PubMed PubMed Citation Articles by Boytim, M. L. Articles by Clayberger, C.

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 Rapamycin¹

Michelle L. Boytim^*, Shu-Chen Lyu^*, Ron Jung^*, Alan M. Krensky and Carol Clayberger^2,*,

^* Department of Cardiothoracic Surgery and Division of Immunology and Transplantation Biology/Department of Pediatrics, Stanford University, Stanford, CA 94305

A synthetic peptide corresponding to a region of the ₁ -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.

This article has been cited by other articles:

				W. Zang, M. Lin, S. Kalache, N. Zhang, B. Kruger, A. M. Waaga-Gasser, M. Grimm, W. Hancock, P. Heeger, B. Schroppel, et al. Inhibition of the Alloimmune Response through the Generation of Regulatory T Cells by a MHC Class II-Derived Peptide J. Immunol., December 1, 2008; 181(11): 7499 - 7506. [Abstract] [Full Text] [PDF]

				R. Bahri, F. Hirsch, A. Josse, N. Rouas-Freiss, N. Bidere, A. Vasquez, E. D. Carosella, B. Charpentier, and A. Durrbach Soluble HLA-G Inhibits Cell Cycle Progression in Human Alloreactive T Lymphocytes J. Immunol., February 1, 2006; 176(3): 1331 - 1339. [Abstract] [Full Text] [PDF]

				W. Zang, S. Kalache, M. Lin, B. Schroppel, and B. Murphy MHC Class II-Mediated Apoptosis by a Nonpolymorphic MHC Class II Peptide Proceeds by Activation of Protein Kinase C J. Am. Soc. Nephrol., December 1, 2005; 16(12): 3661 - 3668. [Abstract] [Full Text] [PDF]

				L. C. Foukas, G. Panayotou, and P. R. Shepherd Direct Interaction of Major Histocompatibility Complex Class II-derived Peptides with Class Ia Phosphoinositide 3-Kinase Results in Dose-dependent Stimulatory Effects J. Biol. Chem., February 27, 2004; 279(9): 7505 - 7511. [Abstract] [Full Text] [PDF]

				C. Dong, S.-C. Lyu, A. M. Krensky, and C. Clayberger DQ 65-79, A Peptide Derived from HLA Class II, Mimics p21 to Block T Cell Proliferation J. Immunol., November 15, 2003; 171(10): 5064 - 5070. [Abstract] [Full Text] [PDF]

				Y. Jiang, D. Chen, S.-C. Lyu, X. Ling, A. M. Krensky, and C. Clayberger DQ 65-79, a Peptide Derived from HLA Class II, Induces I{kappa}B Expression J. Immunol., April 1, 2002; 168(7): 3323 - 3328. [Abstract] [Full Text] [PDF]

				S. Trembleau, S. Gregori, G. Penna, I. Gorny, and L. Adorini IL-12 Administration Reveals Diabetogenic T Cells in Genetically Resistant I-E{alpha}-Transgenic Nonobese Diabetic Mice: Resistance to Autoimmune Diabetes Is Associated with Binding of E{alpha}-Derived Peptides to the I-Ag7 Molecule J. Immunol., October 1, 2001; 167(7): 4104 - 4114. [Abstract] [Full Text] [PDF]

				K. Vos, I. E. van der Horst-Bruinsma, J. M. W. Hazes, F. C. Breedveld, S. le Cessie, G. M. Th. Schreuder, R. R. P. de Vries, and E. Zanelli Evidence for a protective role of the human leukocyte antigen class II region in early rheumatoid arthritis Rheumatology, February 1, 2001; 40(2): 133 - 139. [Abstract] [Full Text] [PDF]

				X. Ling, S. Kamangar, M. L. Boytim, Z. Kelman, P. Huie, S.-C. Lyu, R. K. Sibley, J. Hurwitz, C. Clayberger, and A. M. Krensky Proliferating Cell Nuclear Antigen as the Cell Cycle Sensor for an HLA-Derived Peptide Blocking T Cell Proliferation J. Immunol., June 15, 2000; 164(12): 6188 - 6192. [Abstract] [Full Text] [PDF]

				B. MURPHY and A. M. KRENSKY HLA-Derived Peptides as Novel Immunomodulatory Therapeutics J. Am. Soc. Nephrol., June 1, 1999; 10(6): 1346 - 1355. [Abstract] [Full Text]