Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Amino Acid Sequence
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Animals
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Apoptosis / immunology
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Binding, Competitive / immunology
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Cells, Cultured
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins / chemistry*
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Cyclins / metabolism
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Growth Inhibitors / chemistry*
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Growth Inhibitors / metabolism
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HLA-DQ Antigens / chemistry*
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HLA-DQ Antigens / metabolism
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HLA-DQ alpha-Chains
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Humans
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Mice
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Molecular Mimicry / immunology*
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Molecular Sequence Data
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Peptide Fragments / chemistry*
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Peptide Fragments / metabolism
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Peptide Mapping / methods
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Precipitin Tests
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Proliferating Cell Nuclear Antigen / chemistry*
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Proliferating Cell Nuclear Antigen / metabolism
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Protein Binding
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T-Lymphocyte Subsets / cytology*
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
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Two-Hybrid System Techniques
Substances
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CDKN1A protein, human
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Cdkn1a protein, mouse
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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DQ 65-79
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Growth Inhibitors
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HLA-DQ Antigens
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HLA-DQ alpha-Chains
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HLA-DQA1 antigen
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Peptide Fragments
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Proliferating Cell Nuclear Antigen