DQ 65–79, A Peptide Derived from HLA Class II, Mimics p21 to Block T Cell Proliferation 1

DQ 65–79, a peptide derived from residues 65–79 of the α-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.