DQ 65-79, a peptide derived from HLA class II, induces IκB expression

A synthetic peptide corresponding to residues 65-79 of the α helix of the α-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, IκB-α, whose expression is increased by DQ 65-79. IκB proteins, including IκB-α and IκB-β, are increased in T cells treated with DQ 65-79. Nuclear translocation of the NF-κB 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 IκB-α mRNA and inhibits the activity of IκB kinase. These findings indicate that the DQ 65-79 peptide increases the level of IκB proteins, thereby preventing nuclear translocation of the transcription factor, NF-κB, and inhibiting T cell proliferation.