DQ 65–79, a Peptide Derived from HLA Class II, Induces IκB Expression

Abstract

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.

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“…NFB is a transcriptional regulator that mediates key immune and inflammatory responses [4]. The translocation of NFB to the nucleus, where it can activate transcription of target genes, requires dissociation of IB from the complex that usually involves a three-step process of IB degradation [5]. The IB proteins are first phosphorylated by a family of IB kinases (IKK), which targets IB for ubiquitination and subsequent degradation by the 26S proteasome [6,7].…”

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

“…Both peptides are largely composed of hydrophobic and charged residues. We previously showed that treatment of cells with DQ 65-79 decreases expression of p21 mRNA and protein (9,35). This suggests that there is a feedback loop controlling p21 expression and that DQ 65-79 interferes with that loop.…”