DQ 65-79, a peptide derived from HLA class II, induces I kappa B expression.
A synthetic peptide corresponding to residues 65-79 of the alpha helix of the alpha-chain of the class II HLA molecule DQA03011 (DQ 65-79) inhibits the proliferation of human T lymphocytes in an allele nonrestricted manner. By using microarray technology, we found that expression of 29 genes was increased or decreased in a human CTL cell line after treatment with DQ 65-79. This study focuses on one of these genes, IkappaB-alpha, whose expression is increased by DQ 65-79. IkappaB proteins, including IkappaB-alpha and IkappaB-beta, are increased in T cells treated with DQ 65-79. Nuclear translocation of the NF-kappaB subunits p65 and p50 is decreased in T cells after treatment with DQ 65-79, while elevated levels of p65 and p50 are present in cytosol. DQ 65-79 inhibits the degradation of IkappaB-alpha mRNA and inhibits the activity of IkappaB kinase. These findings indicate that the DQ 65-79 peptide increases the level of IkappaB proteins, thereby preventing nuclear translocation of the transcription factor, NF-kappaB, and inhibiting T cell proliferation.
Jiang
Yun
Y
Department of Cardiothoracic Surgery, Stanford University, Stanford, CA 94305-5164, USA.
Chen
Daniel
D
Lyu
Shu-Chen
SC
Ling
Xuefeng
X
Krensky
Alan M
AM
Clayberger
Carol
C
D000595:Amino Acid Sequence; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004789:Enzyme Activation / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D006683:HLA-DQ Antigens / Q000494:pharmacology*; D006801:Humans; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins; D007166:Immunosuppressive Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D008969:Molecular Sequence Data; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D021381:Protein Transport / Q000276:immunology; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
D004268:DNA-Binding Proteins; C453546:DQ 65-79; D006683:HLA-DQ Antigens; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D007166:Immunosuppressive Agents; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D010446:Peptide Fragments; D012333:RNA, Messenger; D000072000:NF-KappaB Inhibitor alpha; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human