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Targeted Delivery of an Antigenic Peptide to the Endoplasmic Reticulum: Application for Development of a Peptide Therapy for Ankylosing Spondylitis

The development of suitable methods to deliver peptides specifically to the endoplasmic reticulum (ER) can provide some potential therapeutic applications of such peptides. Ankylosing spondylitis (AS) is strongly associated with the expression of human leukocytic antigen-B27 (HLA-B27). HLA-B27 heavy...

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Autores principales: Yu, Hui-Chun, Lu, Ming-Chi, Li, Chin, Huang, Hsien-Lu, Huang, Kuang-Yung, Liu, Su-Qin, Lai, Ning-Sheng, Huang, Hsien-Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796468/
https://www.ncbi.nlm.nih.gov/pubmed/24155957
http://dx.doi.org/10.1371/journal.pone.0077451
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author Yu, Hui-Chun
Lu, Ming-Chi
Li, Chin
Huang, Hsien-Lu
Huang, Kuang-Yung
Liu, Su-Qin
Lai, Ning-Sheng
Huang, Hsien-Bin
author_facet Yu, Hui-Chun
Lu, Ming-Chi
Li, Chin
Huang, Hsien-Lu
Huang, Kuang-Yung
Liu, Su-Qin
Lai, Ning-Sheng
Huang, Hsien-Bin
author_sort Yu, Hui-Chun
collection PubMed
description The development of suitable methods to deliver peptides specifically to the endoplasmic reticulum (ER) can provide some potential therapeutic applications of such peptides. Ankylosing spondylitis (AS) is strongly associated with the expression of human leukocytic antigen-B27 (HLA-B27). HLA-B27 heavy chain (HC) has a propensity to fold slowly resulting in the accumulation of misfolded HLA-B27 HC in the ER, triggering the unfolded protein response, and forming a homodimer, (B27-HC)(2). Natural killer cells and T-helper 17 cells are then activated, contributing to the major pathogenic potentials of AS. The HLA-B27 HC is thus an important target, and delivery of an HLA-B27-binding peptide to the ER capable of promoting HLA-B27 HC folding is a potential mechanism for AS therapy. Here, we demonstrate that a His(6)-ubiquitin-tagged Tat-derived peptide (THU) can deliver an HLA-B27-binding peptide to the ER promoting HLA-B27 HC folding. The THU-HLA-B27-binding peptide fusion protein crossed the cell membrane to the cytosol through the Tat-derived peptide. The HLA-B27-binding peptide was specifically cleaved from THU by cytosolic ubiquitin C-terminal hydrolases and subsequently transported into the ER by the transporter associated with antigen processing. This approach has potential application in the development of peptide therapy for AS.
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spelling pubmed-37964682013-10-23 Targeted Delivery of an Antigenic Peptide to the Endoplasmic Reticulum: Application for Development of a Peptide Therapy for Ankylosing Spondylitis Yu, Hui-Chun Lu, Ming-Chi Li, Chin Huang, Hsien-Lu Huang, Kuang-Yung Liu, Su-Qin Lai, Ning-Sheng Huang, Hsien-Bin PLoS One Research Article The development of suitable methods to deliver peptides specifically to the endoplasmic reticulum (ER) can provide some potential therapeutic applications of such peptides. Ankylosing spondylitis (AS) is strongly associated with the expression of human leukocytic antigen-B27 (HLA-B27). HLA-B27 heavy chain (HC) has a propensity to fold slowly resulting in the accumulation of misfolded HLA-B27 HC in the ER, triggering the unfolded protein response, and forming a homodimer, (B27-HC)(2). Natural killer cells and T-helper 17 cells are then activated, contributing to the major pathogenic potentials of AS. The HLA-B27 HC is thus an important target, and delivery of an HLA-B27-binding peptide to the ER capable of promoting HLA-B27 HC folding is a potential mechanism for AS therapy. Here, we demonstrate that a His(6)-ubiquitin-tagged Tat-derived peptide (THU) can deliver an HLA-B27-binding peptide to the ER promoting HLA-B27 HC folding. The THU-HLA-B27-binding peptide fusion protein crossed the cell membrane to the cytosol through the Tat-derived peptide. The HLA-B27-binding peptide was specifically cleaved from THU by cytosolic ubiquitin C-terminal hydrolases and subsequently transported into the ER by the transporter associated with antigen processing. This approach has potential application in the development of peptide therapy for AS. Public Library of Science 2013-10-14 /pmc/articles/PMC3796468/ /pubmed/24155957 http://dx.doi.org/10.1371/journal.pone.0077451 Text en © 2013 Yu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Yu, Hui-Chun
Lu, Ming-Chi
Li, Chin
Huang, Hsien-Lu
Huang, Kuang-Yung
Liu, Su-Qin
Lai, Ning-Sheng
Huang, Hsien-Bin
Targeted Delivery of an Antigenic Peptide to the Endoplasmic Reticulum: Application for Development of a Peptide Therapy for Ankylosing Spondylitis
title Targeted Delivery of an Antigenic Peptide to the Endoplasmic Reticulum: Application for Development of a Peptide Therapy for Ankylosing Spondylitis
title_full Targeted Delivery of an Antigenic Peptide to the Endoplasmic Reticulum: Application for Development of a Peptide Therapy for Ankylosing Spondylitis
title_fullStr Targeted Delivery of an Antigenic Peptide to the Endoplasmic Reticulum: Application for Development of a Peptide Therapy for Ankylosing Spondylitis
title_full_unstemmed Targeted Delivery of an Antigenic Peptide to the Endoplasmic Reticulum: Application for Development of a Peptide Therapy for Ankylosing Spondylitis
title_short Targeted Delivery of an Antigenic Peptide to the Endoplasmic Reticulum: Application for Development of a Peptide Therapy for Ankylosing Spondylitis
title_sort targeted delivery of an antigenic peptide to the endoplasmic reticulum: application for development of a peptide therapy for ankylosing spondylitis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796468/
https://www.ncbi.nlm.nih.gov/pubmed/24155957
http://dx.doi.org/10.1371/journal.pone.0077451
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