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A cyclic peptide accelerates the loading of peptide antigens in major histocompatibility complex class II molecules.

Abstract：

:Major histocompatibility complex (MHC)-loading enhancers (MLE) have recently attracted attention because of their ability to enhance the efficacy of peptide immunotherapeutics. As small molecular weight compounds, they influence the loading of peptides in MHC molecules by converting them from a non-receptive to a receptive state. Herein, we report a 14-mer cyclic peptide 1 (CP-1) as a new class of MLE-peptide. This peptide was used to investigate its loading on human leukocyte antigen (HLA)-DR molecules. It was found that CP-1 strongly accelerates peptide-loading on both soluble and cell surface HLA-DR molecules in a dose-dependent manner. The effect was evident for all subsets of HLA-DR tested, including HLA-DRB1*1501, indicating that it acts independently of P1-pocket size, which is the canonical MLE-binding site. Importantly, increased peptide-loading by CP-1 was correlated with improved CD4(+) T cell responses in vitro, while propidium iodide staining indicated low peptide-induced cytotoxicity. Thus, this study revealed a new class of peptide-based enhancers that catalyze peptide-loading by allosteric interactions with MHC molecules. Because of its low cellular cytotoxicity and high MLE activity, it may be useful in stimulating antigen-specific T cell responses for therapeutic purposes.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Afridi S,Shaheen F,Roetzschke O,Shah ZA,Abbas SC,Siraj R,Makhmoor T

doi

10.1016/j.bbrc.2014.12.047

subject

Has Abstract

pub_date

2015-01-16 00:00:00

pages

774-9

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(14)02213-X

journal_volume

456

pub_type

杂志文章

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