DQ 65-79, a peptide derived from HLA class II, mimics p21 to block T cell proliferation.
DQ 65-79, a peptide derived from residues 65-79 of the alpha-chain HLA class II molecule DQA03011, blocks T cell proliferation and induces T cell apoptosis. Using a yeast two-hybrid assay, we previously identified proliferating cell nuclear Ag (PCNA) as an intracellular ligand for DQ 65-79. In this study, we show that three regions of PCNA, residues 81-100, 121-140, and 241-261, interact with DQ 65-79. Residues 241-261 of PCNA also interact with the C terminus (residues 139-160) of the cell cycle regulator, p21, suggesting that DQ 65-79 and p21 might function similarly. We show here that DQ 65-79 competitively inhibits binding of p21 to PCNA and that both DQ 65-79 and p21 139-160 induce T cell apoptosis, suggesting that DQ 65-79 and p21 act similarly to inhibit cell growth.
Dong
Chen
C
Division of Immunology and Transplantation Biology, Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
Lyu
Shu-Chen
SC
Krensky
Alan M
AM
Clayberger
Carol
C
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001667:Binding, Competitive / Q000276:immunology; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000737:chemistry* / Q000378:metabolism; D006131:Growth Inhibitors / Q000737:chemistry* / Q000378:metabolism; D006683:HLA-DQ Antigens / Q000737:chemistry* / Q000378:metabolism; D059848:HLA-DQ alpha-Chains; D006801:Humans; D051379:Mice; D018716:Molecular Mimicry / Q000276:immunology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D010449:Peptide Mapping / Q000379:methods; D011233:Precipitin Tests; D018809:Proliferating Cell Nuclear Antigen / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D020798:Two-Hybrid System Techniques
C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; C453546:DQ 65-79; D006131:Growth Inhibitors; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; C069050:HLA-DQA1 antigen; D010446:Peptide Fragments; D018809:Proliferating Cell Nuclear Antigen