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Cited by 24Immunotherapy and Immune ResponsesRNA Interference and Gene DeliveryAdvancements in Transdermal Drug Delivery

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A membrane penetrating multiple antigen peptide (MAP) incorporating ovalbumin CD8 epitope induces potent immune responses in mice

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Brooks, Nicole A., Pouniotis, Dodie S., Sheng, Kuo-Ching, Apostolopoulos, Vasso, Pietersz, Geoffrey A.·2010·Biochimica et Biophysica Acta (BBA) - Biomembranes
DOI 10.1016/j.bbamem.2010.05.007
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Abstract

Cell penetrating peptides (CPP) represent a novel approach to facilitate cytoplasmic delivery of macromolecules. The DNA binding domain of Drosophila Antennapedia contains 60 amino acids and consists of 3 α-helices, with internalizing activity mapped to a 16-amino acid peptide penetratin (Antp) within the third α-helix. Here, we report on the use of penetratin to deliver a multiple antigen peptide (MAP) incorporating the immunodominant CD8 epitope of ovalbumin, SIINFEKL (MAPOVACD8). We demonstrate that penetratin linked to the MAPOVACD8 construct either by a disulfide (SS) or thioether (SC) linkage promotes the uptake, cross presentation and subsequent in vivo proliferation and generation of OVACD8 (SIINFEKL)-specific T cells. The MAPOVACD8 construct without penetratin is not presented by MHC class I molecules nor does it generate an in vivo IFN-γ response in C57BL/6 mice. Moreover, we clearly define the uptake and intracellular processing pathways of AntpMAPOVACD8 SS and SC revealing the majority of AntpMAPOVACD8 is taken up by DC via an endocytic, proteasome and tapasin independent mechanism. We also show that the uptake mechanism of AntpMAPOVACD8 is dose dependent and uptake or intracellular processing is not altered by the type of chemical linkage.

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References 30 · Cited by 24

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Metadata

Authors
Brooks, N. A., Pouniotis, D. S., Sheng, K.-C., Apostolopoulos, V., & Pietersz, G. A.
Affiliations
  • Burnet Institute (AU)
  • RMIT University (AU)
ORCID
Venue
Biochimica et Biophysica Acta (BBA) - Biomembranes
Publisher
Elsevier BV
Published
2010-12
Volume
1798
Issue
12
Pages
2286-2295
ISSN
0005-2736 (ISSN-L)
DOI
10.1016/j.bbamem.2010.05.007
OpenAlex
W1972085403
Cited by
24
References
30
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2019: 1 · 2018: 4 · 2016: 1 · 2015: 4 · 2014: 3 · 2013: 2 · 2012: 2
FWCI
0.82
Type
journal article
Language
en
Open access
Licence
Locations
  • Biochimica et Biophysica Acta (BBA) - Biomembranes (publishedVersion)
  • PubMed (publishedVersion)
  • RMIT Research Repository (RMIT University Library) (submittedVersion)
  • Figshare (submittedVersion)
  • Griffith Research Online (submittedVersion)
Funders
  • Cancer Council Victoria
  • National Health and Medical Research Council
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
Keywords
cell-penetrating peptides, penetratin, multiple antigen peptide, SIINFEKL, antigen delivery, dendritic cell uptake, cross-presentation, MHC class I antigen presentation, T cell proliferation, intracellular processing, endocytosis, proteasome, thioether linkage, disulfide bonds, IFN-gamma response
MeSH terms
Animals, Epitopes, Carrier Proteins, Dendritic Cells, Dose-Response Relationship, Drug, Dose-Response Relationship, Immunologic, Drosophila, Endocytosis, Interferon-gamma, Ovalbumin, T-Lymphocytes, Histocompatibility Antigens Class I, Protein Structure, Secondary, Antigen Presentation, Membrane Transport Proteins, Proteasome Endopeptidase Complex, Cell Proliferation, Mice, Cell-Penetrating Peptides

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