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

被引:21
作者
Brooks, Nicole A. [2 ]
Pouniotis, Dodie S. [2 ]
Sheng, Kuo-Ching [3 ]
Apostolopoulos, Vasso [3 ]
Pietersz, Geoffrey A. [1 ]
机构
[1] Burnet Inst, Bioorgan & Med Chem Lab, Melbourne, Vic 3004, Australia
[2] RMIT Univ, Sch Med Sci, Melbourne, Vic, Australia
[3] Burnet Inst, Immunol & Vaccine Lab, Melbourne, Vic 3004, Australia
来源
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES | 2010年 / 1798卷 / 12期
基金
澳大利亚国家健康与医学研究理事会;
关键词
Cell penetrating peptides; Penetratin; Cancer vaccines; Multiple antigen peptide; Antigen presentation; T-CELL RESPONSES; DENDRITIC CELLS; PROTEIN TRANSDUCTION; CANCER VACCINES; CTL EPITOPES; DELIVERY; PATHWAY; PROMISE;
D O I
10.1016/j.bbamem.2010.05.007
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 alpha-helices, with internalizing activity mapped to a 16-amino acid peptide penetratin (Antp) within the third alpha-helix. Here, we report on the use of penetratin to deliver a multiple antigen peptide (MAP) incorporating the immunodominant COB 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-gamma 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. (C) 2010 Elsevier B.V. All rights reserved.
引用
收藏
页码:2286 / 2295
页数:10
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